AGE

, Volume 36, Issue 1, pp 313–351 | Cite as

Thymus and aging: morphological, radiological, and functional overview

  • Rita Rezzani
  • Lorenzo Nardo
  • Gaia Favero
  • Michele Peroni
  • Luigi Fabrizio Rodella
Article

Abstract

Aging is a continuous process that induces many alterations in the cytoarchitecture of different organs and systems both in humans and animals. Moreover, it is associated with increased susceptibility to infectious, autoimmune, and neoplastic processes. The thymus is a primary lymphoid organ responsible for the production of immunocompetent T cells and, with aging, it atrophies and declines in functions. Universality of thymic involution in all species possessing thymus, including human, indicates it as a long-standing evolutionary event. Although it is accepted that many factors contribute to age-associated thymic involution, little is known about the mechanisms involved in the process. The exact time point of the initiation is not well defined. To address the issue, we report the exact age of thymus throughout the review so that readers can have a nicely pictured synoptic view of the process. Focusing our attention on the different stages of the development of the thymus gland (natal, postnatal, adult, and old), we describe chronologically the morphological changes of the gland. We report that the thymic morphology and cell types are evolutionarily preserved in several vertebrate species. This finding is important in understanding the similar problems caused by senescence and other diseases. Another point that we considered very important is to indicate the assessment of the thymus through radiological images to highlight its variability in shape, size, and anatomical conformation.

Keywords

Aging Human Rodent Thymus 

Notes

Acknowledgments

The authors sincerely thank CHRONOLIFE S.r.l. for the support of this study and Miss Castrezzati Stefania for her technical support.

References

  1. Abe K, Ito T (1970) Fine structure of small lymphocytes in the thymus of the mouse: qualitative and quantitative analysis by electron microscopy. Z Zellforsch Mikrosk Anat 110:321–335PubMedGoogle Scholar
  2. Ackman JB, Wu CC (2011) MRI of the thymus. AJR Am J Roentgenol 197:W15–W20PubMedGoogle Scholar
  3. Ahima RS, Prabakaran D, Mantzoros C, Qu D, Lowell B, Maratos-Flier E, Flier JS (1996) Role of leptin in the neuroendocrine response to fasting. Nature 382:250–252PubMedGoogle Scholar
  4. Ahsan F, Allison R, White J (2010) Ectopic cervical thymus: case report and review of pathogenesis and management. J Laryngol Otol 124:694–697PubMedGoogle Scholar
  5. al-Shawaf AA, Kendall MD, Cowen T (1991) Identification of neural profiles containing vasoactive intestinal polypeptide, acetylcholinesterase and catecholamines in the rat thymus. J Anat 174:131–143PubMedGoogle Scholar
  6. Altintas MM, Nayer B, Walford EC, Johnson KB, Gaidosh G, Reiser J, De La Cruz-Munoz N, Ortega LM, Nayer A (2012) Leptin deficiency-induced obesity affects the density of mast cells in abdominal fat depots and lymph nodes in mice. Lipids Health Dis 11:21PubMedCentralPubMedGoogle Scholar
  7. Anderson M, Anderson SK, Farr AG (2000) Thymic vasculature: organizer of the medullary epithelial compartment? Int Immunol 12:1105–1110PubMedGoogle Scholar
  8. Appay V, Sauce D, Prelog M (2010) The role of the thymus in immunosenescence: lessons from the study of thymectomized individuals. Aging (Albany NY) 2:78–81Google Scholar
  9. Ardavín C (1997) Thymic dendritic cells. Immunol Today 18:350–361PubMedGoogle Scholar
  10. Ardavín C, Martínez del Hoyo G, Martín P, Anjuère F, Arias CF, Marín AR, Ruiz S, Parrillas V, Hernández H (2001) Origin and differentiation of dendritic cells. Trends Immunol 22:691–700PubMedGoogle Scholar
  11. Ardavin C, Wu L, Li CL, Shortman K (1993) Thymic dendritic cells and T cells develop simultaneously in the thymus from a common precursor population. Nature 362:761–763PubMedGoogle Scholar
  12. Aspinall R, Andrew D (2000) Thymic involution in aging. J Clin Immunol 20:250–256PubMedGoogle Scholar
  13. Aw D, Palmer DB (2012) It's not all equal: a multiphasic theory of thymic involution. Biogerontology 13:77–81PubMedGoogle Scholar
  14. Aw D, Silva AB, Maddick M, von Zglinicki T, Palmer DB (2008) Architectural changes in the thymus of aging mice. Aging Cell 7:158–167PubMedGoogle Scholar
  15. Aw D, Silva AB, Palmer DB (2007) Immunosenescence: emerging challenges for an ageing population. Immunology 120:435–446PubMedGoogle Scholar
  16. Aw D, Silva AB, Palmer DB (2010) The effect of age on the phenotype and function of developing thymocytes. J Comp Pathol 142(Suppl 1):S45–S59PubMedGoogle Scholar
  17. Aw D, Taylor-Brown F, Cooper K, Palmer DB (2009) Phenotypical and morphological changes in the thymic microenvironment from ageing mice. Biogerontology 10:311–322PubMedGoogle Scholar
  18. Barger JL, Walford RL, Weindruch R (2003) The retardation of aging by caloric restriction: its significance in the transgenic era. Exp Gerontol 38:1343–1351PubMedGoogle Scholar
  19. Bauer ME, Jeckel CM, Luz C (2009) The role of stress factors during aging of the immune system. Ann N Y Acad Sci 1153:139–152PubMedGoogle Scholar
  20. Bearman RM, Bensch KG, Levine GD (1975) The normal human thymic vasculature: an ultrastructural study. Anat Rec 183:485–497PubMedGoogle Scholar
  21. Bellinger DL, Felten SY, Felten DL (1988) Maintenance of noradrenergic sympathetic innervation in the involuted thymus of the aged Fischer 344 rat. Brain Behav Immunol 2:133–150Google Scholar
  22. Bellinger DL, Lorton D, Felten SY, Felten DL (1992) Innervation of lymphoid organs and implications in development, aging, and autoimmunity. Int J Immunopharmacol 14:329–344PubMedGoogle Scholar
  23. Bennett AR, Farley A, Blair NF, Gordon J, Sharp L, Blackburn CC (2002) Identification and characterization of thymic epithelial progenitor cells. Immunity 16:803–814PubMedGoogle Scholar
  24. Benveniste MF, Rosado-de-Christenson ML, Sabloff BS, Moran CA, Swisher SG, Marom EM (2011) Role of imaging in the diagnosis, staging, and treatment of thymoma. Radiographics 31:1847–1861, discussion 1861–1863PubMedGoogle Scholar
  25. Berthelot JM, le Goff B, Maugars Y (2010) Thymic Hassall's corpuscles, regulatory T-cells, and rheumatoid arthritis. Semin Arthritis Rheumaforsch 39:347–355Google Scholar
  26. Blackburn CC, Augustine CL, Li R, Harvey RP, Malin MA, Boyd RL, Miller JF, Morahan G (1996) The nu gene acts cell-autonomously and is required for differentiation of thymic epithelial progenitors. Proc Natl Acad Sci U S A 93:5742–5746PubMedCentralPubMedGoogle Scholar
  27. Boehm T, Bleul CC (2007) The evolutionary history of lymphoid organs. Nat Immunol 8:131–135PubMedGoogle Scholar
  28. Bravo-Nuevo A, O'Donnell R, Rosendahl A, Chung JH, Benjamin LE, Odaka C (2011) RhoB deficiency in thymic medullary epithelium leads to early thymic atrophy. Int Immunol 23:593–600PubMedGoogle Scholar
  29. Brelińska R (2003) Thymic epithelial cells in age-dependent involution. Microsc Res Tech 62:488–500PubMedGoogle Scholar
  30. Brelińska R, Jaroszewicz A, Kowalska K (2002a) Age-related changes in rat thymic epithelial cells. Folia Histochem Cytobiol 40:173–174PubMedGoogle Scholar
  31. Brelińska R, Ostalska D, Kaczmarek E, Kowalska K (2002b) Stages of the rat thymic medulla development in foetal period. Folia Histochem Cytobiol 40:171–172PubMedGoogle Scholar
  32. Brelińska R, Warchol JB (1997) Thymic nurse cells: their functional ultrastructure. Microsc Res Tech 38:250–266PubMedGoogle Scholar
  33. Brimnes MK, Jensen T, Jørgensen TN, Michelsen BK, Troelsen J, Werdelin O (2002) Low expression of insulin in the thymus of non-obese diabetic mice. J Autoimmun 19:203–213PubMedGoogle Scholar
  34. Bryson JL, Coles MC, Manley NR (2011) A method for labeling vasculature in embryonic mice. J Vis Exp (56). pii: 3267Google Scholar
  35. Buckland J, Pennington DJ, Bruno L, Owen MJ (2000) Co-ordination of the expression of the protein tyrosine kinase p56(lck) with the pre-T cell receptor during thymocyte development. Eur J Immunol 30:8–18PubMedGoogle Scholar
  36. Bulckaen H, Prévost G, Boulanger E, Robitaille G, Roquet V, Gaxatte C, Garçon G, Corman B, Gosset P, Shirali P, Creusy C, Puisieux F (2008) Low-dose aspirin prevents age-related endothelial dysfunction in a mouse model of physiological aging. Am J Physiol Heart Circ Physiol 294:H1562–H1570PubMedGoogle Scholar
  37. Bulloch K, McEwen BS, Diwa A, Radojcic T, Hausman J, Baird S (1994) The role of calcitonin gene-related peptide in the mouse thymus revisited. Ann N Y Acad Sci 741:129–136PubMedGoogle Scholar
  38. Bulloch K, Pomerantz W (1984) Autonomic nervous system innervation of thymic-related lymphoid tissue in wildtype and nude mice. J Comp Neurol 228:57–68PubMedGoogle Scholar
  39. Büyükyavuz I, Otçu S, Karnak I, Akçören Z, Senocak ME (2002) Ectopic thymic tissue as a rare and confusing entity. Eur J Pediatr Surg 2:327–329Google Scholar
  40. Cahill DR (1998) Anomalous thymic branch of the right common carotid artery. Clin Anat 11:346–348PubMedGoogle Scholar
  41. Castle SC (2000) Impact of age-related immune dysfunction on risk of infections. Z Gerontol Geriatr 33:341–349PubMedGoogle Scholar
  42. Cavallotti C, Artico M, Cavallotti D (1999) Occurrence of adrenergic nerve fibers and of noradrenaline in thymus gland of juvenile and aged rats. Immunol Lett 70:53–62PubMedGoogle Scholar
  43. Cavallotti C, D'Andrea V, Tonnarini G, Cavallotti C, Bruzzone P (2008) Age-related changes in the human thymus studied with scanning electron microscopy. Microsc Res Tech 71:573–578PubMedGoogle Scholar
  44. Celli J, Duijf P, Hamel BC, Bamshad M, Kramer B, Smits AP, Newbury-Ecob R, Hennekam RC, Van Buggenhout G, van Haeringen A, Woods CG, van Essen AJ, de Waal VG, Haber DA, Yang A, McKeon F, Brunner HG, van Bokhoven H (1999) Heterozygous germline mutations in the p53 homolog p63 are the cause of EEC syndrome. Cell 99:143–153PubMedGoogle Scholar
  45. Chen L, Xiao S, Manley NR (2009) Foxn1 is required to maintain the postnatal thymic microenvironment in a dosage-sensitive manner. Blood 113:567–574PubMedGoogle Scholar
  46. Chen Y, Qiao S, Tuckermann J, Okret S, Jondal M (2010) Thymus-derived glucocorticoids mediate androgen effects on thymocyte homeostasis. FASEB J 24:5043–5051PubMedGoogle Scholar
  47. Chinn IK, Blackburn CC, Manley NR, Sempowski GD (2012) Changes in primary lymphoid organs with aging. Semin Immunol 24:309–320PubMedCentralPubMedGoogle Scholar
  48. Chowhan AK, Kinnera VS, Yootla M, Reddy MK (2010) Cervical ectopic thymus masquerading as metastatic thyroid papillary carcinoma. Malays J Pathol 32:65–68PubMedGoogle Scholar
  49. Csorba TR, Lyon AW, Hollenberg MD (2010) Autoimmunity and the pathogenesis of type 1 diabetes. Crit Rev Clin Lab Sci 47:51–71PubMedGoogle Scholar
  50. Cuddihy AR, Ge S, Zhu J, Jang J, Chidgey A, Thurston G, Boyd R, Crooks GM (2009) VEGF-mediated cross-talk within the neonatal murine thymus. Blood 113:2723–2731PubMedGoogle Scholar
  51. Dakic A, Shao QX, D'Amico A, O'Keeffe M, Chen WF, Shortman K, Wu L (2004) Development of the dendritic cell system during mouse ontogeny. J Immunol 172:1018–1027PubMedGoogle Scholar
  52. Deitch EA, Ananthakrishnan P, Cohen DB, Xu da Z, Feketeova E, Hauser CJ (2006) Neutrophil activation is modulated by sex hormones after trauma-hemorrhagic shock and burn injuries. Am J Physiol Heart Circ Physiol 291:H1456–H1465Google Scholar
  53. den Braber I, Mugwagwa T, Vrisekoop N, Westera L, Mögling R, de Boer AB, Willems N, Schrijver EH, Spierenburg G, Gaiser K, Mul E, Otto SA, Ruiter AF, Ackermans MT, Miedema F, Borghans JA, de Boer RJ, Tesselaar K (2012) Maintenance of peripheral naive T cells is sustained by thymus output in mice but not humans. Immunity 36:288–297Google Scholar
  54. Di Marino V, Argème M, Brunet C, Coppens R, Bonnoit J (1987) Macroscopic study of the adult thymus. Surg Radiol Anat 9:51–62PubMedGoogle Scholar
  55. Dixit VD (2012) Impact of immune-metabolic interactions on age-related thymic demise and T cell senescence. Semin Immunol 24(5):321–330PubMedGoogle Scholar
  56. Dooley J, Liston A (2012) Molecular control over thymic involution: from cytokines and microRNA to aging and adipose tissue. Eur J Immunol 42:1073–1079Google Scholar
  57. Douagi I, André I, Ferraz JC, Cumano A (2000) Characterization of T cell precursor activity in the murine fetal thymus: evidence for an input of T cell precursors between days 12 and 14 of gestation. Eur J Immunol 30:2201–2210PubMedGoogle Scholar
  58. Krishna MJV, Subhadra VD (2012) Morphological features of human thymus glands from foetal to old age. Int J Biol Med Res 3:1502–1505Google Scholar
  59. Ebbesen P, Christensen HE (1972) Foa-Kurloff cells in the Hassal bodies of oestrogenized guinea-pigs. Acta Pathol Microbiol Scand A 80:600–602PubMedGoogle Scholar
  60. Ezaki T, Uehara Y (1997) Thymic nurse cells forming a dynamic microenvironment in spontaneous thymoma BUF/Mna rats. Arch Histol Cytol 60:39–51PubMedGoogle Scholar
  61. Fabris N, Mocchegiani E, Provinciali M (1997) Plasticity of neuro-endocrine-thymus interactions during aging--a minireview. Cell Mol Biol (Noisy-le-grand) 43:529–541Google Scholar
  62. Fatani JA, Qayyum MA, Mehta L, Singh U (1986) Parasympathetic innervation of the thymus: a histochemical and immunocytochemical study. J Anat 147:115–119PubMedGoogle Scholar
  63. Fedorova ES, Poliakova VO, Konovalov SS, Kvetnoĭ IM (2009) Expression of serotonin and vessel endothelial growth factor (VEGF) in human thymus in aging involution. Adv Gerontol 22:167–171PubMedGoogle Scholar
  64. Fernandes G, Handwerger BS, Yunis EJ, Brown DM (1978) Immune response in the mutant diabetic C57BL/Ks-dt + mouse. Discrepancies between in vitro and in vivo immunological assays. J Clin Invest 61:243–250PubMedCentralPubMedGoogle Scholar
  65. Ferrando-Martínez S, Ruiz-Mateos E, Hernández A, Gutiérrez E, Rodríguez-Méndez Mdel M, Ordoñez A, Leal M (2011) Age-related deregulation of naive T cell homeostasis in elderly humans. Age (Dordr) 33:197–207Google Scholar
  66. Flegal KM, Graubard BI, Williamson DF, Gail MH (2006) Weight and mortality. Hypertension 47:e6PubMedGoogle Scholar
  67. Flegal KM, Graubard BI, Williamson DF, Gail MH (2007) Cause-specific excess deaths associated with underweight, overweight, and obesity. JAMA 298:2028–2037PubMedGoogle Scholar
  68. Flomerfelt FA, El Kassar N, Gurunathan C, Chua KS, League SC, Schmitz S, Gershon TR, Kapoor V, Yan XY, Schwartz RH, Gress RE (2010) Tbata modulates thymic stromal cell proliferation and thymus function. J Exp Med 207:2521–2532PubMedCentralPubMedGoogle Scholar
  69. Flores KG, Li J, Sempowski GD, Haynes BF, Hale LP (1999) Analysis of the human thymic perivascular space during aging. J Clin Invest 104:1031–1039PubMedCentralPubMedGoogle Scholar
  70. Forsberg JG (2000) Neonatal estrogen treatment and its consequences for thymus development, serum level of autoantibodies to cardiolipin, and the delayed-type hypersensitivity response. J Toxicol Environ Health A 60:185–213PubMedGoogle Scholar
  71. Foster K, Sheridan J, Veiga-Fernandes H, Roderick K, Pachnis V, Adams R, Blackburn C, Kioussis D, Coles M (2008) Contribution of neural crest-derived cells in the embryonic and adult thymus. J Immunol 180:3183–3189PubMedGoogle Scholar
  72. Franceschi C, Bonafè M (2003) Centenarians as a model for healthy aging. Biochem Soc Trans 31:457–461PubMedGoogle Scholar
  73. Fujita Y, Murakami M, Ogawa Y, Masuzaki H, Tanaka M, Ozaki S, Nakao K, Mimori T (2002) Leptin inhibits stress-induced apoptosis of T lymphocytes. Clin Exp Immunol 128:21–26PubMedCentralPubMedGoogle Scholar
  74. Gawande RS, Khurana A, Messing S, Zhang D, Castañeda RT, Goldsby RE, Hawkins RA, Daldrup-Link HE (2012) Differentiation of normal thymus from anterior mediastinal lymphoma and lymphoma recurrence at pediatric PET/CT. Radiology 262:613–622PubMedGoogle Scholar
  75. Ghali WM, Abdel-Rahman S, Nagib M, Mahran ZY (1980) Intrinsic innervation and vasculature of pre- and post-natal human thymus. Acta Anat (Basel) 108:115–123Google Scholar
  76. Gill J, Malin M, Holländer GA, Boyd R (2002) Generation of a complete thymic microenvironment by MTS24(+) thymic epithelial cells. Nat Immunol 3:635–642PubMedGoogle Scholar
  77. Goldberg GL, Sutherland JS, Hammet MV, Milton MK, Heng TS, Chidgey AP, Boyd RL (2005) Sex steroid ablation enhances lymphoid recovery following autologous hematopoietic stem cell transplantation. Transplantation 80:1604–1613PubMedGoogle Scholar
  78. Goldman KP, Park CS, Kim M, Matzinger P, Anderson CC (2005) Thymic cortical epithelium induces self tolerance. Eur J Immunol 35:709–717PubMedGoogle Scholar
  79. Gray D, Abramson J, Benoist C, Mathis D (2007) Proliferative arrest and rapid turnover of thymic epithelial cells expressing Aire. J Exp Med 204:2521–2528PubMedCentralPubMedGoogle Scholar
  80. Gray DH, Seach N, Ueno T, Milton MK, Liston A, Lew AM, Goodnow CC, Boyd RL (2006) Developmental kinetics, turnover, and stimulatory capacity of thymic epithelial cells. Blood 108:3777–3785PubMedGoogle Scholar
  81. Gray DH, Ueno T, Chidgey AP, Malin M, Goldberg GL, Takahama Y, Boyd RL (2005) Controlling the thymic microenvironment. Curr Opin Immunol 17:137–143PubMedGoogle Scholar
  82. Griffith AV, Fallahi M, Venables T, Petrie HT (2012) Persistent degenerative changes in thymic organ function revealed by an inducible model of organ regrowth. Aging Cell 11:169–177PubMedGoogle Scholar
  83. Gruia AT, Barbu-Tudoran L, Mic AA, Ordodi VL, Paunescu V, Mic FA (2011) Arachidonic acid accumulates in the stromal macrophages during thymus involution in diabetes. Histochem Cell Biol 136:79–92PubMedGoogle Scholar
  84. Gui J, Mustachio LM, Su DM, Craig RW (2012) Thymus Size and Age-related Thymic Involution: Early Programming, Sexual Dimorphism, Progenitors and Stroma. Aging Dis 3:280–290PubMedCentralPubMedGoogle Scholar
  85. Gui J, Zhu X, Dohkan J, Cheng L, Barnes PF, Su DM (2007) The aged thymus shows normal recruitment of lymphohematopoietic progenitors but has defects in thymic epithelial cells. Int Immunol 19:1201–1211PubMedGoogle Scholar
  86. Hannestad J, García-Suárez O, Huerta JJ, Esteban I, Naves FJ, Vega JA (1997) TrkA neutrophin receptor protein in the rat and human thymus. Anat Rec 249:373–379PubMedGoogle Scholar
  87. Haslam DW, James WP (2005) Obesity. Lancet 366:1197–1209PubMedGoogle Scholar
  88. Haynes BF, Sempowski GD, Wells AF, Hale LP (2000) The human thymus during aging. Immunol Res 22:253–261PubMedGoogle Scholar
  89. Heng TS, Goldberg GL, Gray DH, Sutherland JS, Chidgey AP, Boyd RL (2005) Effects of castration on thymocyte development in two different models of thymic involution. J Immunol 175:2982–2993PubMedGoogle Scholar
  90. Herman TE, Siegel MJ (2009) Cervical ectopic thymus. J Perinatol 29:173–174PubMedGoogle Scholar
  91. Hernández-López C, Varas A, Sacedón R, Martínez VG, Hidalgo L, Valencia J, Zapata AG, Vicente A (2010) The CXCL12/CXCR4 pair in aged human thymus. Neuroimmunomodulation 17:217–220PubMedGoogle Scholar
  92. Hick RW, Gruver AL, Ventevogel MS, Haynes BF, Sempowski GD (2006) Leptin selectively augments thymopoiesis in leptin deficiency and lipopolysaccharide- induced thymic atrophy. J Immunol 177:169–176PubMedCentralPubMedGoogle Scholar
  93. Hince M, Sakkal S, Vlahos K, Dudakov J, Boyd R, Chidgey A (2008) The role of sex steroids and gonadectomy in the control of thymic involution. Cell Immunol 252:122–138PubMedGoogle Scholar
  94. Hirokawa K, Saitoh K, Hatakeyama S (1983) Enzyme histochemical study on human thymus and its age change. Acta Pathol Jpn 33:275–285PubMedGoogle Scholar
  95. Hofer J, Hofer S, Zlamy M, Jeller V, Koppelstaetter C, Brandstätter A, Kern H, Köhle J, Zimmerhackl LB, Prelog M (2009) Elevated proportions of recent thymic emigrants in children and adolescents with type 1 diabetes. Rejuvenation Res 12:311–320PubMedGoogle Scholar
  96. Holland AM, van den Brink MR (2009) Rejuvenation of the aging T cell compartment. Curr Opin Immunol 21:454–459PubMedCentralPubMedGoogle Scholar
  97. Holländer GA, Krenger W, Blazar BR (2010) Emerging strategies to boost thymic function. Curr Opin Pharmacol 10:443–453PubMedCentralPubMedGoogle Scholar
  98. Ichimiya S, Kojima T (2006) Cellular networks of human thymic medullary stromas coordinated by p53-related transcription factors. J Histochem Cytochem 54:1277–1289PubMedGoogle Scholar
  99. Inaoka T, Takahashi K, Mineta M, Yamada T, Shuke N, Okizaki A, Nagasawa K, Sugimori H, Aburano T (2007) Thymic hyperplasia and thymus gland tumors: differentiation with chemical shift MR imaging. Radiology 243:869–876PubMedGoogle Scholar
  100. Irla M, Guenot J, Sealy G, Reith W, Imhof BA, Sergé A (2013) Three-dimensional visualization of the mouse thymus organization in health and immunodeficiency. J Immunol 190:586–596PubMedGoogle Scholar
  101. Ito T, Hoshino T (1996) Light and electron microscopic observations on the vascular pattern of the thymus of the mouse. Arch Histol Jpn 27:351–361Google Scholar
  102. Itoi M, Kawamoto H, Katsura Y, Amagai T (2001) Two distinct steps of immigration of hematopoietic progenitors into the early thymus anlage. Int Immunol 13:1203–1211PubMedGoogle Scholar
  103. Jenkinson WE, Bacon A, White AJ, Anderson G, Jenkinson EJ (2008) An epithelial progenitor pool regulates thymus growth. J Immunol 181:6101–6108PubMedGoogle Scholar
  104. Kaitaniemi S, Grön K, Elovaara H, Salmi M, Jalkanen S, Elima K (2013) Functional modulation of vascular adhesion protein-1 by a novel splice variant. PLoS One 8:e54151PubMedCentralPubMedGoogle Scholar
  105. Kang N, Duan L, Tang L, Liu S, Li C, Li Y, Liu Q, Hu Y, Cui L, He W (2008) Identification and characterization of a novel thymus aging related protein Rwdd1. Cell Mol Immunol 5:279–285PubMedGoogle Scholar
  106. Kato M, Hara M, Ozawa Y, Shimizu S, Shibamato Y (2012) Computed tomography and magnetic resonance imaging features of posterior mediastinal ganglioneuroma. J Thorac Imaging 27:100–106PubMedGoogle Scholar
  107. Kato S (1997) Thymic microvascular system. Microsc Res Tech 38:287–299PubMedGoogle Scholar
  108. Kato S, Schoefl GI (1987) The vasculature of the guinea-pig thymus: topographic studies by light and electron microscopy. Arch Histol Jpn 50:299–314PubMedGoogle Scholar
  109. Kato S, Schoefl GI (1989) Microvasculature of normal and involuted mouse thymus. Light- and electron-microscopic study. Acta Anat (Basel) 135:1–11Google Scholar
  110. Kelley KW, Weigent DA, Kooijman R (2007) Protein hormones and immunity. Brain Behav Immun 21:384–392PubMedCentralPubMedGoogle Scholar
  111. Kim HG, Kim MJ, Lee MJ (2012) Sonographic appearance of intrathyroid ectopic thymus in children. J Clin Ultrasound 40:266–271PubMedGoogle Scholar
  112. Kissenpfennig A, Aït-Yahia S, Clair-Moninot V, Stössel H, Badell E, Bordat Y, Pooley JL, Lang T, Prina E, Coste I, Gresser O, Renno T, Winter N, Milon G, Shortman K, Romani N, Lebecque S, Malissen B, Saeland S, Douillard P (2005) Disruption of the langerin/CD207 gene abolishes Birbeck granules without a marked loss of Langerhans cell function. Mol Cell Biol 25:88–99PubMedCentralPubMedGoogle Scholar
  113. Kittas C, Parsons MA, Henry L (1979) A light and electron microscope study on the origin of Foà-Kurloff cells. Br J Exp Pathol 60:276–285PubMedCentralPubMedGoogle Scholar
  114. Klug DB, Carter C, Crouch E, Roop D, Conti CJ, Richie ER (1998) Interdependence of cortical thymic epithelial cell differentiation and T-lineage commitment. Proc Natl Acad Sci U S A 95:11822–11827PubMedCentralPubMedGoogle Scholar
  115. Koo GC, Peppard JR, Hatzfeld A (1982) Ontogeny of Nk-1+ natural killer cells. I. Promotion of Nk-1+ cells in fetal, baby, and old mice. J Immunol 129:867–871PubMedGoogle Scholar
  116. Kotani M, Kawakita M, Fukanogi M, Yamashita A, Seiki K (1967) The passage of thymic lymphocytes to the circulation in the rat. Okajimas Folia Anat Jpn 43:61–71PubMedGoogle Scholar
  117. Kuwabara H, Krenacs T, Hirano H, Nishio H, Shikata T, Kizaki T, Nagai M, Suzuki K, Mori H (2002) Immunolocalization of peripheral lymph node addressins in normal and neoplastic human thymuses. Appl Immunohistochem Mol Morphol 10:253–257Google Scholar
  118. Kvell K, Varecza Z, Bartis D, Hesse S, Parnell S, Anderson G, Jenkinson EJ, Pongracz JE (2010) Wnt4 and LAP2alpha as pacemakers of thymic epithelial senescence. PLoS One 5:e10701PubMedCentralPubMedGoogle Scholar
  119. Lafontaine M, Landry D, Montplaisir S (1997) Human thymic dendritic cells. Microsc Res Tech 38:267–275PubMedGoogle Scholar
  120. Law LW, Dunn TB, Trainin N, Levey RH (1964) Studies of thymic function. Wistar Inst Symp Monogr 2:105–120PubMedGoogle Scholar
  121. Laws AM, Osborne BA (2004) p53 regulates thymic Notch1 activation. Eur J Immunol 34(3):726–734PubMedGoogle Scholar
  122. Lee CK, Kim JK, Kim Y, Lee MK, Kim K, Kang JK, Hofmeister R, Durum SK, Han SS (2001) Generation of macrophages from early T progenitors in vitro. J Immunol 166:5964–5969PubMedGoogle Scholar
  123. Lepique AP, Palencia S, Irjala H, Petrie HT (2003) Characterization of vascular adhesion molecules that may facilitate progenitor homing in the post-natal mouse thymus. Clin Dev Immunol 10:27–33PubMedCentralPubMedGoogle Scholar
  124. Levi-Montalcini R, Skaper SD, Dal Toso R, Petrelli L, Leon A (1996) Nerve growth factor: from neurotrophin to neurokine. Trends Neurosci 19:514–520PubMedGoogle Scholar
  125. Liu D, Kitajima M, Awai K, Nakayama Y, Tamura Y, Suda H, Asonuma K, Inomata Y, Yamashita Y (2006) Ectopic cervical thymus in an infant. Radiat Med 24:452–455PubMedGoogle Scholar
  126. Liu LT, Lang ZF, Li Y, Zhu YJ, Zhang JT, Guo SF, Wang JX, Wang HW, Xu YD (2013) Composition and characteristics of distinct macrophage subpopulations in themou se thymus. Mol Med Rep 7:1850–1854PubMedGoogle Scholar
  127. Lynch HE, Goldberg GL, Chidgey A, Van den Brink MR, Boyd R, Sempowski GD (2009) Thymic involution and immune reconstitution. Trends Immunol 30:366–373PubMedCentralPubMedGoogle Scholar
  128. Madden KS, Thyagarajan S, Felten DL (1998) Alterations in sympathetic noradrenergic innervation in lymphoid organs with age. Ann N Y Acad Sci 840:262–268PubMedGoogle Scholar
  129. Manley NR, Richie ER, Blackburn CC, Condie BG, Sage J (2011) Structure and function of the thymic microenvironment. Front Biosci 16:2461–2477Google Scholar
  130. Marinova TT, Spassov LD, Vlassov VI, Pashev VV, Markova MD, Ganev VS, Dzhupanova RS, Angelov DN (2009) Aged human thymus hassall's corpuscles are immunoreactive for IGF-I and IGF-I receptor. Anat Rec (Hoboken) 292:960–965Google Scholar
  131. Marinova T, Velikova K, Philipov S, Stankulov I, Chaldakov G, Aloe L (2003) Cellular localization of NGF and NGF receptors in aged human thymus. Folia Biol (Praha) 49:160–164.Google Scholar
  132. Matarese G, Moschos S, Mantzoros CS (2005) Leptin in immunology. J Immunol 174:3137–3142PubMedGoogle Scholar
  133. Meilin A, Shoham J, Schreiber L, Sharabi Y (1995) The role of thymocytes in regulating thymic epithelial cell growth and function. Scand J Immunol 42:185–190PubMedGoogle Scholar
  134. Mello Coelho V, Bunbury A, Rangel LB, Giri B, Weeraratna A, Morin PJ, Bernier M, Taub DD (2009) Fat-storing multilocular cells expressing CCR5 increase in the thymus with advancing age: potential role for CCR5 ligands on the differentiation and migration of preadipocytes. Int J Med Sci 7:1–14PubMedCentralPubMedGoogle Scholar
  135. Mignini F, Streccioni V, Amenta F (2003) Autonomic innervation of immune organs and neuroimmune modulation. Auton Autacoid Pharmacol 23:1–25PubMedGoogle Scholar
  136. Milićević NM, Milićević Z (2004) Thymus cell-cell interactions. Int Rev Cytol 235:1–52PubMedGoogle Scholar
  137. Milićević NM, Milićević Z, Colic M, Mujović S (1987) Ultrastructural study of macrophages in the rat thymus, with special reference to the cortico-medullary zone. J Anat 150:89–98PubMedGoogle Scholar
  138. Milićević NM, Milićević Z, Piletić O, Mujović S, Ninkov V (1983) Reactivity of thymic metallophilic cells during the regeneration after the application of cyclophosphamide. J Reticuloendothel Soc 34:501–507PubMedGoogle Scholar
  139. Milićević NM, Milićević ZJ (1984) Enzyme-histochemical characterization of macrophages in the rat thymus, with special reference to metallophilic cells of the corticomedullary zone. J Leukoc Biol 36:761–769PubMedGoogle Scholar
  140. Miller JF (2002) The discovery of thymus function and of thymus-derived lymphocytes. Immunol Rev 185:7–14PubMedGoogle Scholar
  141. Miller RA, Harper JM, Galecki A, Burke DT (2002) Big mice die young: early life body weight predicts longevity in genetically heterogeneous mice. Aging Cell 1:22–29PubMedGoogle Scholar
  142. Miller JFAP, Marshall AHE, White RG (1962) The immunological significance of the thymus. Adv Immunol 2:111–162Google Scholar
  143. Min D, Panoskaltsis-Mortari A, Kuro-O M, Holländer GA, Blazar BR, Weinberg KI (2007) Sustained thymopoiesis and improvement in functional immunity induced by exogenous KGF administration in murine models of aging. Blood 109:2529–2537PubMedGoogle Scholar
  144. Min H, Montecino-Rodriguez E, Dorshkind K (2006) Reassessing the role of growth hormone and sex steroids in thymic involution. Clin Immunol 118:117–123PubMedGoogle Scholar
  145. Mitchell B, Kendall M, Adam E, Schumacher U (1997) Innervation of the thymus in normal and bone marrow reconstituted severe combined immunodeficient (SCID) mice. J Neuroimmunol 75:19–27PubMedGoogle Scholar
  146. Mitchell WA, Lang PO, Aspinall R (2010) Tracing thymic output in older individuals. Clin Exp Immunol 161:497–503PubMedCentralPubMedGoogle Scholar
  147. Mizia-Malarz A, Sobol G, Maldyk J, Stolpa W, Szyszka A, Wos H (2009) Cervical ectopic thymus in a 9-month-old girl: diagnostic difficulties. J Pediatr Hematol Oncol 31:599–601PubMedGoogle Scholar
  148. Mocchegiani E, Santarelli L, Costarelli L, Cipriano C, Muti E, Giacconi R, Malavolta M (2006) Plasticity of neuroendocrine-thymus interactions during ontogeny and ageing: role of zinc and arginine. Ageing Res Rev 5:281–309PubMedGoogle Scholar
  149. Mori K, Itoi M, Tsukamoto N, Amagai T (2010) Foxn1 is essential for vascularization of the murine thymus anlage. Cell Immunol 260:66–69PubMedGoogle Scholar
  150. Mori K, Itoi M, Tsukamoto N, Kubo H, Amagai T (2007) The perivascular space as a path of hematopoietic progenitor cells and mature T cells between the blood circulation and the thymic parenchyma. Int Immunol 19:745–753PubMedGoogle Scholar
  151. Morley JE (2003) Hormones and the aging process. J Am Geriatr Soc 51:S333–S337PubMedGoogle Scholar
  152. Morrhaye G, Kermani H, Legros JJ, Baron F, Beguin Y, Moutschen M, Cheynier R, Martens HJ, Geenen V (2009) Impact of growth hormone (GH) deficiency and GH replacement upon thymus function in adult patients. PLoS One 22:e5668Google Scholar
  153. Müller SM, Stolt CC, Terszowski G, Blum C, Amagai T, Kessaris N, Iannarelli P, Richardson WD, Wegner M, Rodewald HR (2008) Neural crest origin of perivascular mesenchyme in the adult thymus. J Immunol 180:5344–5351PubMedGoogle Scholar
  154. Nabarra B, Andrianarison I (1996) Ultrastructural study of thymic microenvironment involution in aging mice. Exp Gerontol 31:489–506PubMedGoogle Scholar
  155. Naquet P, Naspetti M, Boyd R (1999) Development, organization and function of the thymic medulla in normal, immunodeficient or autoimmune mice. Semin Immunol 11:47–55PubMedGoogle Scholar
  156. Nasseri F, Eftekhari F (2010) Clinical and radiologic review of the normal and abnormal thymus: pearls and pitfalls. Radiographics 30:413–428PubMedGoogle Scholar
  157. Nehls M, Pfeifer D, Schorpp M, Hedrich H, Boehm T (1994) New member of the winged-helix protein family disrupted in mouse and rat nude mutations. Nature 372:103–107PubMedGoogle Scholar
  158. Neumann CG, Gewa C, Bwibo NO (2004) Child nutrition in developing countries. Pediatr Ann 33:658–674PubMedGoogle Scholar
  159. Niijima A (1995) An electrophysiological study on the vagal innervation of the thymus in the rat. Brain Res Bull 38:319–323PubMedGoogle Scholar
  160. Olsen NJ, Viselli SM, Fan J, Kovacs WJ (1998) Androgens accelerate thymocyte apoptosis. Endocrinology 139:748–752PubMedGoogle Scholar
  161. Opiela SJ, Koru-Sengul T, Adkins B (2009) Murine neonatal recent thymic emigrants are phenotypically and functionally distinct from adult recent thymic emigrants. Blood 113:5635–5643PubMedGoogle Scholar
  162. Ortega E, Garcia JJ, De La Fuente M (2000) Ageing modulates some aspects of the non-specific immune response of murine macrophages and lymphocytes. Exp Physiol 85:519–525PubMedGoogle Scholar
  163. Ortman CL, Dittmar KA, Witte PL, Le PT (2002) Molecular characterization of the mouse involuted thymus: aberrations in expression of transcription regulators in thymocyte and epithelial compartments. Int Immunol 14:813–822PubMedGoogle Scholar
  164. Papadopoulou AS, Dooley J, Linterman MA, Pierson W, Ucar O, Kyewski B, Zuklys S et al (2012) The thymic epithelial microRNA network elevates the threshold for infection-associated thymic involution via suppression of the IFN-α receptor mediated by microRNA-29 a. Nat Immunol 13:181–187Google Scholar
  165. Petrie HT (2002) Role of thymic organ structure and stromal composition in steady-state postnatal T-cell production. Immunol Rev 189:8–19PubMedGoogle Scholar
  166. Pereira G, Clermont Y (1971) Distribution of cell web-containing epithelial reticular cells in the rat thymus. Anat Rec 169:613–626PubMedGoogle Scholar
  167. Pond CM (2000) Adipose tissue: quartermaster to the lymph node garrisons. Biologist 47:147–150PubMedGoogle Scholar
  168. Prasad TR, Chui CH, Ong CL, Meenakshi A (2006) Cervical ectopic thymus in an infant. Singap Med J 47:68–70Google Scholar
  169. Qiao S, Chen L, Okret S, Jondal M (2008) Age-related synthesis of glucocorticoids in thymocytes. Exp Cell Res 314:3027–3035PubMedGoogle Scholar
  170. Ranlov P, Christensen HE, Wanstrup J (1970) Effects of thymectomy upon the formation of Fóa-Kurloff cells in the guinea pig. Acta Pathol Microbiol Scand B Microbiol Immunol 78:330–332PubMedGoogle Scholar
  171. Raviola E, Karnovsky MJ (1972) Evidence for a blood-thymus barrier using electron-opaque tracers. J Exp Med 136:466–498PubMedCentralPubMedGoogle Scholar
  172. Revest JM, Suniara RK, Kerr K, Owen JJ, Dickson C (2001) Development of the thymus requires signaling through the fibroblast growth factor receptor R2-IIIb. J Immunol 167:1954–1961PubMedGoogle Scholar
  173. Rezzani R, Bonomini F, Rodella LF (2008) Histochemical and molecular overview of the thymus as site for T-cells development. Prog Histochem Cytochem 43:73–120PubMedGoogle Scholar
  174. Rezzani R, Rodella L, Zauli G, Caimi L, Vitale M (1999) Mouse peritoneal cells as a reservoir of late dendritic cell progenitors. Br J Haematol 104:111–118PubMedGoogle Scholar
  175. Rode I, Boehm T (2012) Regenerative capacity of adult cortical thymic epithelial cells. Proc Natl Acad Sci U S A 109:3463–3468PubMedCentralPubMedGoogle Scholar
  176. Rodewald HR (2008) Thymus organogenesis. Annu Rev Immunol 26:355–388PubMedGoogle Scholar
  177. Rodewald HR, Paul S, Haller C, Bluethmann H, Blum C (2001) Thymus medulla consisting of epithelial islets each derived from a single progenitor. Nature 414:763–768PubMedGoogle Scholar
  178. Rose MR, Flatt T, Graves JL, Greer LF, Martinez DE, Matos M, Mueller LD, Shmookler Reis RJ, Shahrestani P (2012) What is Aging? Front Genet 3:134PubMedCentralPubMedGoogle Scholar
  179. Safadi FF, Dissanayake IR, Goodman GG, Jago RA, Baker AE, Bowman AR, Sass DA, Popoff SN, Epstein S (2000) Influence of estrogen deficiency and replacement on T-cell populations in rat lymphoid tissues and organs. Endocrine 2:81–88Google Scholar
  180. Safieddine N, Keshavjee S (2011) Anatomy of the thymus gland. Thorac Surg Clin 21:191–195PubMedGoogle Scholar
  181. Saggese D, Ceroni Compadretti G, Cartaroni C (2002) Cervical ectopic thymus: a case report and review of the literature. Int J Pediatr Otorhinolaryngol 66:77–80PubMedGoogle Scholar
  182. Sakai S, Murayama S, Soeda H, Matsuo Y, Ono M, Masuda K (2002) Differential diagnosis between thymoma and non-thymoma by dynamic MR imaging. Acta Radiol 43:262–268PubMedGoogle Scholar
  183. Salas J, Montiel M, Jiménez E, Valenzuela M, Valderrama JF, Castillo R, González S, El Bekay R (2009) Angiogenic properties of adult human thymus fat. Cell Tissue Res 338:313–318Google Scholar
  184. Samms M, Martinez M, Fousse S, Pezzano M, Guyden JC (2001) Circulating macrophages as well as developing thymocytes are enclosed within thymic nurse cells. Cell Immunol 212:16–23PubMedGoogle Scholar
  185. Savchenko AS, Hasegawa G, Naito M (2006) Development and maturation of thymic dendritic cells during human ontogeny. Cell Tissue Res 325:455–460PubMedGoogle Scholar
  186. Savino W (2002) The thymus gland is a target in malnutrition. Eur J Clin Nutr 56:S46–S49PubMedGoogle Scholar
  187. Savino W, Boitard C, Bach JF, Dardenne M (1991) Studies on the thymus in nonobese diabetic mouse. I. Changes in the microenvironmental compartments. Lab Invest 64:405–417PubMedGoogle Scholar
  188. Savino W, de Mello-Coelho V, Dardenne M (1995) Control of the thymic microenvironment by growth hormone/insulin-like growth factor-I-mediated circuits. Neuroimmunomodulation 2:313–318PubMedGoogle Scholar
  189. Schluep M, Willcox N, Ritter MA, Newsom-Davis J, Larché M, Brown AN (1988) Myasthenia gravis thymus: clinical, histological and culture correlations. J Autoimmun 1:445–467PubMedGoogle Scholar
  190. Sempowski GD, Hale LP, Sundy JS, Massey JM, Koup RA, Douek DC, Patel DD, Haynes BF (2000) Leukemia inhibitory factor, oncostatin M, IL-6, and stem cell factor mRNA expression in human thymus increases with age and is associated with thymic atrophy. J Immunol 164:2180–2187PubMedGoogle Scholar
  191. Shanley DP, Aw D, Manley NR, Palmer DB (2009) An evolutionary perspective on the mechanisms of immunosenescence. Trends Immunol 30:374–381PubMedGoogle Scholar
  192. Shortman K, Caux C (1997) Dendritic cell development: multiple pathways to nature's adjuvants. Stem Cells 15:409–419PubMedGoogle Scholar
  193. Sminia T, van Asselt AA, van de Ende MB, Dijkstra CD (1986) Rat thymus macrophages: an immunohistochemical study on fetal, neonatal and adult thymus. Thymus 8:141–150PubMedGoogle Scholar
  194. Stämpfli SF, Akhmedov A, Gebhard C, Lohmann C, Holy EW, Rozenberg I, Spescha R, Shi Y, Lüscher TF, Tanner FC, Camici GG (2010) Aging induces endothelial dysfunction while sparing arterial thrombosis. Arterioscler Thromb Vasc Biol 30:1960–1967PubMedGoogle Scholar
  195. Sutherland JS, Goldberg GL, Hammett MV, Uldrich AP, Berzins SP, Heng TS, Blazar BR, Millar JL, Malin MA, Chidgey AP, Boyd RL (2005) Activation of thymic regeneration in mice and humans following androgen blockade. J Immunol 175:2741–2753PubMedGoogle Scholar
  196. Takahashi K, Al-Janabi NJ (2010) Computed tomography and magnetic resonance imaging of mediastinal tumors. J Magn Reson Imaging 32:1325–1339PubMedGoogle Scholar
  197. Takeoka Y, Chen SY, Yago H, Boyd R, Suehiro S, Shultz LD, Ansari AA, Gershwin ME (1996) The murine thymic microenvironment: changes with age. Int Arch Allergy Immunol 111:5–12PubMedGoogle Scholar
  198. Taub DD, Longo DL (2005) Insights into thymic aging and regeneration. Immunol Rev 205:72–93PubMedGoogle Scholar
  199. Taub DD, Murphy WJ, Longo DL (2010) Rejuvenation of the aging thymus: Growth hormone-mediated and ghrelin-mediated signaling pathways. Curr Opin Pharmacol 10:408–424PubMedCentralPubMedGoogle Scholar
  200. Tilg H, Moschen AR (2006) Adipocytokines: mediators linking adipose tissue, inflammation and immunity. Nat Rev Immunol 6:772–783PubMedGoogle Scholar
  201. Tinahones F, Salas J, Mayas MD, Ruiz-Villalba A, Macias-Gonzalez M, Garrido-Sanchez L, DeMora M, Moreno-Santos I, Bernal R, Cardona F, El Bekay R (2009) VEGF gene expression in adult human thymus fat: a correlative study with hypoxic induced factor and cyclooxygenase-2. PLoS One 4:e8213PubMedCentralPubMedGoogle Scholar
  202. Tollefson L, Bulloch K (1990) Dual-label retrograde transport: CNS innervation of the mouse thymus distinct from other mediastinum viscera. J Neurosci Res 25:20–28PubMedGoogle Scholar
  203. Torroba M, Zapata AG (2003) Aging of the vertebrate immune system. Microsc Res Tech 62:477–481PubMedGoogle Scholar
  204. Trotter-Mayo RN, Roberts MR (2008) Leptin acts in the periphery to protect thymocytes from glucocorticoid-mediated apoptosis in the absence of weight loss. Endocrinology 149:5209–5218PubMedGoogle Scholar
  205. Trottier MD, Naaz A, Li Y, Fraker PJ (2012) Enhancement of hematopoiesis and lymphopoiesis in diet-induced obese mice. Proc Natl Acad Sci U S A 109:7622–7629PubMedCentralPubMedGoogle Scholar
  206. Uddin MN, Nishio N, Ito S, Suzuki H, Isobe K (2012) Autophagic activity in thymus and liver during aging. Age (Dordr) 34:75–85Google Scholar
  207. Ushiki T (1986) A scanning electron-microscopic study of the rat thymus with special reference to cell types and migration of lymphocytes into the general circulation. Cell Tissue Res 244:285–298Google Scholar
  208. Utsuyama M, Hirokawa K (1989) Hypertrophy of the thymus and restoration of immune functions in mice and rats by gonadectomy. Mech Ageing Dev 47:175–185PubMedGoogle Scholar
  209. Valladeau J, Ravel O, Dezutter-Dambuyant C, Moore K, Kleijmeer M, Liu Y, Duvert-Frances V, Vincent C, Schmitt D, Davoust J, Caux C, Lebecque S, Saeland S (2000) Langerin, a novel C-type lectin specific to Langerhans cells, is an endocytic receptor that induces the formation of Birbeck granules. Immunity 12:71–81PubMedGoogle Scholar
  210. Van Haelst UJ (1969) Light and electron microscopic study of the normal and pathological thymus of the rat. 3. A mesenchymal histiocytic type of cell. Z Zellforsch Mikrosk Anat 99:198–209PubMedGoogle Scholar
  211. Varas A, Sacedón R, Hernandez-López C, Jiménez E, García-Ceca J, Arias-Díaz J, Zapata AG, Vicente A (2003) Age-dependent changes in thymic macrophages and dendritic cells. Microsc Res Tech 62:501–507PubMedGoogle Scholar
  212. Vicente A, Varas A, Sacedón R, Zapata AG (1996) Histogenesis of the epithelial component of rat thymus: an ultrastructural and immunohistological analysis. Anat Rec 244:506–519PubMedGoogle Scholar
  213. Virts EL, Thoman ML (2010) Age-associated changes in miRNA expression profiles in thymopoiesis. Mech Ageing Dev 131:743–748PubMedCentralPubMedGoogle Scholar
  214. von Gaudecker B (1997) Progressive widening of the mesodermal perivascular space in human thymus. Verh Anat Ges 71:783–787, Pt 1Google Scholar
  215. von Gaudecker B, Kendall MD, Ritter MA (1997) Immuno-electron microscopy of the thymic epithelial microenvironment. Microsc Res Tech 38:237–249Google Scholar
  216. Vremec D, Pooley J, Hochrein H, Wu L, Shortman K (2000) CD4 and CD8 expression by dendritic cell subtypes in mouse thymus and spleen. J Immunol 164:2978–2986PubMedGoogle Scholar
  217. Vremec D, Zorbas M, Scollay R, Saunders DJ, Ardavin CF, Wu L, Shortman K (1992) The surface phenotype of dendritic cells purified from mouse thymus and spleen: investigation of the CD8 expression by a subpopulation of dendritic cells. J Exp Med 176:47–58PubMedGoogle Scholar
  218. Wakimoto T, Tomisaka R, Nishikawa Y, Sato H, Yoshino T, Takahashi K (2008) Identification and characterization of human thymic cortical dendritic macrophages that may act as professional scavengers of apoptotic thymocytes. Immunobiology 213:837–847PubMedGoogle Scholar
  219. Wang J, Fu H, Yang H, Wang L, He Y (2011) Clinical management of cervical ectopic thymus in children. J Pediatr Surg 46:e33–e36PubMedGoogle Scholar
  220. Wu AJ, Hua H, Munson SH, McDevitt HO (2002) Tumor necrosis factor-alpha regulation of CD4 + CD25+ T cell levels in NOD mice. Proc Natl Acad Sci U S A 99:12287–12292PubMedCentralPubMedGoogle Scholar
  221. Wu L, Shortman K (2005) Heterogeneity of thymic dendritic cells. Semin Immunol 17:304–312PubMedGoogle Scholar
  222. Wu L, Vremec D, Ardavin C, Winkel K, Süss G, Georgiou H, Maraskovsky E, Cook W, Shortman K (1995) Mouse thymus dendritic cells: kinetics of development and changes in surface markers during maturation. Eur J Immunol 25:418–425PubMedGoogle Scholar
  223. Xaus J, Comalada M, Barrachina M, Herrero C, Goñalons E, Soler C, Lloberas J, Celada A (2000) The expression of MHC class II genes in macrophages is cell cycle dependent. J Immunol 165:6364–6371PubMedGoogle Scholar
  224. Xing L, Guo J, Tang J, Tang Y, Wang X (1998) Morphological evidence for the location of calcitonin gene-related peptide (CGRP) immunoreactivity in rat lymphocytes. Cell Vis 5:8–12PubMedGoogle Scholar
  225. Yagi H, Nakamura M, Ishii T, Kasahara S, Itoh T (1997) Ultrastructural analysis of mouse thymocyte subpopulations. Eur J Immunol 27:2680–2687PubMedGoogle Scholar
  226. Yamasaki M (1989) Studies on the thyroid and thymic arteries of Japanese adults and fetuses. Anat Anz 169:213–221PubMedGoogle Scholar
  227. Yan SX, Wei W (2011) Castration reverses immunosenescence in aged mice. Acta Pharmacol Sin 32:1085–1086PubMedGoogle Scholar
  228. Yang H, Youm YH, Dixit VD (2009a) Inhibition of thymic adipogenesis by caloric restriction is coupled with reduction in age-related thymic involution. J Immunol 183:3040–3052PubMedCentralPubMedGoogle Scholar
  229. Yang H, Youm YH, Sun Y, Rim JS, Galbán CJ, Vandanmagsar B, Dixit VD (2009b) Axin expression in thymic stromal cells contributes to an age-related increase in thymic adiposity and is associated with reduced thymopoiesis independently of ghrelin signaling. J Leukoc Biol 85:928–938PubMedGoogle Scholar
  230. Yang H, Youm YH, Vandanmagsar B, Rood J, Kumar KG, Butler AA, Dixit VD (2009c) Obesity accelerates thymic aging. Blood 114:3803–3812PubMedGoogle Scholar
  231. Youm YH, Yang H, Amin R, Smith SR, Leff T, Dixit VD (2010) Thiazolidinedione treatment and constitutive-PPARgamma activation induces ectopic adipogenesis and promotes age-related thymic involution. Aging Cell 9:478–489PubMedCentralPubMedGoogle Scholar
  232. Zeira M, Gallily R (1990) Effect of strain and age on in vitro proliferation of murine thymus-derived macrophages. Thymus 15:1–13PubMedGoogle Scholar
  233. Zhang ZL, Constantinou D, Mandel TE, Georgiou HM (1994) Lymphocyte subsets in thymus and peripheral lymphoid tissues of aging and diabetic NOD mice. Autoimmunity 17:41–48PubMedGoogle Scholar
  234. Zhao H, Tian Z, Hao J, Chen B (2005) Extragonadal aromatization increases with time after ovariectomy in rats. Reprod Biol Endocrinol 3:6PubMedCentralPubMedGoogle Scholar
  235. Zieliński M, Kuzdzal J, Szlubowski A, Soja J (2004) Comparison of late results of basic transsternal and extended transsternal thymectomies in the treatment of myasthenia gravis. Ann Thorac Surg 78:253–258Google Scholar

Copyright information

© American Aging Association 2013

Authors and Affiliations

  • Rita Rezzani
    • 1
  • Lorenzo Nardo
    • 2
  • Gaia Favero
    • 1
  • Michele Peroni
    • 1
  • Luigi Fabrizio Rodella
    • 1
  1. 1.Anatomy and Physiopathology Division, Department of Clinical and Experimental SciencesBresciaItaly
  2. 2.Department of Radiology and Biomedical ImagingUniversity of California San FranciscoSan FranciscoUSA

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