Brock DB, Guralnik JM, Brody JA: Demography and epidemiology of aging in the United States In Handbook of the Biology of Aging, 3rd ed., EL Schneider and JW Rowe (eds). (New York, Academic Press, 1990), pp. 3-23.
Scollay RG, Butcher EC, Weissman IL: Thymus cell migration. Quantitative aspects of cellular traffic from the thymus to the periphery in mice. Eur J Immunol 10:210-218, 1980.
Mackall CL, Fleisher TA, Brown MR, Andrich MP, Chen CC, Feuerstein IM, Horowitz ME, Magrath IT, Shad AT, Steinberg SM, et al: Age, thymopoiesis, and CD4+ T-lymphocyte regeneration after intensive chemotherapy. N Engl J Med 332:143-149, 1995.
Douek DC, McFarland RD, Keiser PH, Gage EA, Massey JM, Haynes BF, Polis MA, Haase AT, Feinberg MB, Sullivan JL, Jamieson BD, Zack JA, Picker LJ, Koup RA: Changes in thymic function with age and during the treatment of HIV infection. Nature 396:690-695, 1998.
Kampinga J, Groen H, Klatter FA, Pater JM, van Petersen AS, Roser B, Nieuwenhuis P, Aspinall R: Post-thymic T-cell development in the rat. Thymus 24:173-200, 1997.
Hulstaert F, Hannet I, Deneys V, Munhyeshuli V, Reichert T, De Bruyere M, Strauss K: Age-related changes in human blood lymphocyte subpopulations. II. Varying kinetics of percentage and absolute count measurements. Clin Immunol Immunopathol 70:152-158, 1994.
Utsuyama M, Hirokawa K: Age-related changes of splenic T cells in mice—A flow cytometric analysis. Mech Ageing Dev 40:89-102, 1987.
Perillo NL, Walford RL, Newman MA, Effros RB: Human T lymphocytes possess a limited in vitro life span. Exp Gerontol 24:177-187, 1989.
Pawelec G, Rehbein A, Haehnel K, Merl A, Adibzadeh M: Human T-cell clones in long-term culture as a model of immunosenescence. Immunol Rev 160:31-42, 1997.
Effros RB, Pawelec G: Replicative senescence of T cells: Does the Hayflick limit lead to immune exhaustion? Immunology Today 18:450-454, 1997.
Murasko DM, Weiner P, Kaye D: Decline in mitogen induced proliferation of lymphocytes with increasing age. Decline in mitogen induced proliferation of lymphocytes with increasing age. Clin Exp Immunol 70:440-448, 1987.
Hobbs MV, Weigle WO, Noonan DJ, Torbett BE, McEvilly RJ, Koch RJ, Cardenas GJ, Ernst DN: Patterns of cytokine gene expression by CD4— T cells from young and old mice. J Immunol 150 150:3602-3614, 1993.
Jackola DR, Ruger JK, Miller RA: Age-associated changes in human T cell phenotype and function. Aging Milano 6:25-34, 1994.
Engwerda CR, Handwerger BS, Fox BS: Aged T cells are hyporesponsive to costimulation mediated by CD28. J Immunol 152:3740-3747, 1994.
Nociari MM, Telford W, Russo C: Postthymic development of CD282CD81 T cell subset: Age-associated expansion and shift from memory to naive phenotype. J Immunol 162:3327-3335, 1999.
Quadri RA, Plastre O, Phelouzat MA, Arbogast A, Proust JJ: Age-related tyrosine-specific protein phosphorylation defect in human T lymphocytes activated through CD3, CD4, CD8 or the IL-2 receptor. Mech Ageing Dev 88:125-138, 1996.
Whisler RL, Newhouse YG, Bagenstose SE: Age-related reductions in the activation of mitogen-activated protein kinases p44mapk/ERK1 and p42mapk/ERK2 in human T cells stimulated via ligation of the T cell receptor complex. Cell Immunol 168:201-210, 1996.
Quadri RA, Arbogast A, Phelouzat MA, Boutet S, Plastre O, Proust JJ: Age-associated decline in cdk1 activity delays cell cycle progression of human T lymphocytes. J Immunol 161:5203-5209, 1998.
Engwerda CR, Fox BS, Handwerger BS: Cytokine production by T lymphocytes from young and aged mice. J Immunol 156:3621-3630, 1996.
Hobbs MV, Ernst DN, Torbett BE, Glasebrook AL, Rehse MA, McQuitty DN, Thoman ML, Bottomly K, Rothermel AL, Noonan DJ, et al: Cell proliferation and cytokine production by CD4+ cells from old mice. J Cell Biochem 46:312-320, 1991.
Steinmann GG: Changes in the human thymus during aging. Curr Top Pathol 75:43-88, 1986.
Kendall MD, Johnson HR, Singh J: The weight of the human thymus gland at necropsy. J Anat 131:483-497, 1980.
Bertho JM, Demarquay C, Moulian N, Van De Meeren A, Berrih-Akhnin S, Gourmelon P: Phenotypic and immunohistological analyses of the human adult thymus: Evidence for an active thymus during adult life. Cell Immunol 179:30-40, 1997.
Aspinall R: Age-associated thymic atrophy in the mouse is due to a deficiency affecting rearrangement of the TCR during intrathymic T cell development. J Immunol 158:3037-3045, 1997.
Wu L, Scollay R, Egerton M, Pearse M, Spangrude GJ, Shortman K: CD4 expressed on earliest T-lineage precursor cells in the adult murine thymus. Nature 349:71-74, 1991.
Rahemtulla A, Fung Leung WP, Schilham MW, Kundig TM, Sambhara SR, Narendran A, Arabian A, Wakeham A, Paige CJ, Zinkernagel RM, et al: Normal development and function of CD8+ cells but markedly decreased helper cell activity in mice lacking CD4. Nature 353:180-184, 1991.
Dudley EC, Petrie HT, Shah LM, Owen MJ, Hayday AC: T cell receptor beta chain gene rearrangement and selection during thymocyte development in adult mice. Immunity 1:83-93, 1994.
Su DM, Wang J, Lin Q, Cooper MD, Watanabe T: Interferons alpha/beta inhibit IL-7-induced proliferation of CD4-CD8-CD-CD44+CD25+ thymocytes, but do not inhibit that of CD4-CD8-CD3-CD44-CD25- thymocytes. Immunology 90:543-549, 1997.
Godfrey DI, Kennedy J, Suda T, Zlotnik A: A developmental pathway involving four phenotypically and functionally distinct subsets of CD3-CD4-CD8- triple-negative adult mouse thymocytes defined by CD44 and CD25 expression. J Immunol 150: 4244-4252, 1993.
Godfrey DI, Kennedy J, Mombaerts P, Tonegawa S, Zlotnik A: Onset of TCR-beta gene rearrangement and role of TCR-beta expression during CD3-CD4-CD8- thymocyte differentiation. J Immunol 152:4783-4792, 1994.
Moore TA, Zlotnik A: T-cell lineage commitment and cytokine responses of thymic progenitors. Blood 86:1850-1860, 1995.
Alam SM, Travers PJ, Wung JL, Nasholds W, Redpath S, Jameson SC, Gascoigne NR: T-cell-receptor affinity and thymocyte positive selection. Nature 381:616-620, 1996.
Brandle D, Muller C, Rulicke T, Hengartner H, Pircher H: Engagement of the T-cell receptor during positive selection in the thymus down-regulates RAG-1 expression. Proc Natl Acad Sci USA 89:9529-9533, 1992.
Petrie HT, Livak F, Schatz DG, Strasser A, Crispe IN, Shortman K: Multiple rearrangements in T cell receptor alpha chain genes maximize the production of useful thymocytes. J Exp Med 178:615-622, 1993.
Jameson SC, Hogquist KA, Bevan MJ: Positive selection of thymocytes. Annu Rev Immunol 13:93-126, 1995.
Penit C, Vasseur F: Expansion of mature thymocyte subsets before emigration to the periphery. J Immunol 159:4848-4856, 1997.
Mamalaki C, Elliot J, Norton T, Yannoutsos N, Townsend AR, Chandler P, Simpson E, Kioussis D: Positive and negative selection in transgenic mice expressing a T-cell receptor specific for influenza nucleoprotein and endogenous superantigen. Dev Immunol 3:159-174, 1993.
Lacorazza HD, Patino JAG, Weksler ME, Radu D, Nikolic-Zugic J: Failure of rearranged TCR transgenes to prevent age-associated thymic involution. J Immunol 163:4262-4268, 1999.
Tyan ML: Age-related decrease in mouse T cell progenitors. J Immunol 118:846-851, 1977.
Tyan ML: Impaired thymic regeneration in lethally irradiated mice given bone marrow from aged donors. Proc Soc Exp Biol Med 152:33-35, 1976.
Mackall CL, Punt JA, Morgan P, Farr AG, Gress RE: Thymic function in young/old chimeras: Substantial thymic T cell regenerative capacity despite irreversible age-associated thymic involution. Eur J Immunol 28:1886-1893, 1998.
Doria G, Mancini C, Utsuyama M, Frasca D, Hirokawa K: Aging of the recipients but not of the bone marrow donors enhances autoimmunity in syngeneic radiation chimeras. Mech Ageing Dev 95:131-142, 1997.
Yu S, Abel L, Globerson A: Thymocyte progenitors and T cell development in aging. Mech Ageing Dev 94:103-111, 1997.
Sharp A, Kukulansky T, Globerson A: In vitro analysis of age-related changes in the developmental potential of bone marrow thymocyte progenitors. Eur J Immunol 20:2541-2546, 1990.
Mackall CL, Gress RE: Thymic aging and T-cell regeneration. Immunol Rev 160:91-102, 1997.
Penit C, Lucas B, Vasseur F, Rieker T, Boyd RL: Thymic medulla epithelial cells acquire specific markers by post-mitotic maturation. Dev Immunol 5:25-36, 1996.
Shores EW, van Ewijk W, Singer A: Maturation of medullary thymic epithelium requires thymocytes expressing fully assembled CD3-TCR complexes. Int Immunol 6:1393-1402, 1994.
Hartwig M, Steinmann G: On a causal mechanism of chronic thymic involution in man. Mech Ageing Dev 75:151-156, 1994.
Haynes BF, Shimizu K, Eisenbarth GS: Identification of human and rodent thymic epithelium using tetanus toxin and monoclonal antibody A2B5. J Clin Invest 71:9-14, 1983.
Klug DB, Carter C, Crouch E, Roop D, Conti CJ, Richie ER: Interdependence of cortical thymic epithelial cell differentiation and T-lineage commitment. Proc Natl Acad Sci USA 95:11822-11827, 1998.
Farr AG, Rudensky A: Medullary thymic epithelium: a mosaic of epithelial “self”? J Exp Med 188:1-4, 1998.
Porcellini S, Panigada M, Grassi F: Molecular and cellular aspects of induced thymus development in recombinase-deficient mice. Eur J Immunol 29:2476-2483, 1999.
Anderson KL, Moore NC, McLoughlin DE, Jenkinson EJ, Owen JJ: Studies on thymic epithelial cells in vitro. Dev Comp Immunol 22:367-377, 1998.
Wynford Thomas D: Proliferative life span checkpoints: Cell-type specificity and influence on tumour biology. Eur J Cancer 33:716-726, 1997.
Dimri GP, Lee X, Basile G, Acosta M, Scott G, Roskelley C, Medrano EE, Linskens M, Rubelj I, Pereira Smith O, et al: A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc Natl Acad Sci USA 92:9363-9367, 1995.
Smith JR, Pereira Smith OM: Replicative senescence: Implications for in vivo aging and tumor suppression. Science 273:63-67, 1996.
Farr AG, Sidman CL: Reduced expression of Ia antigens by thymic epithelial cells of aged mice. J Immunol 133:98-103, 1984.
Bhatia SK, Tygrett LT, Grabstein KH, Waldschmidt TJ: The effect of in vivo IL-7 deprivation on T cell maturation. J Exp Med 181:1399-1409, 1995.
Crompton T, Outram SV, Buckland J, Owen MJ: A transgenic T cell receptor restores thymocyte differentiation in interleukin-7 receptor α chain deficient mice. Eur J Immunol 27:100-104, 1997.
Muegge K, Vila MP, Durum SK: Interleukin-7: A cofactor for V(D)J rearrangement of the T cell receptor beta gene. Science 261:93-95, 1993.
Tsuda S, Rieke S, Hashimoto Y, Nakauchi H, Takahama Y: IL-7 supports D-J but not V-DJ rearrangement of TCR-beta gene in fetal liver progenitor cells. J Immunol 156:3233-3242, 1996.
Oosterwegel MA, Haks MC, Jeffry U, Murray R, Kruisbeek AM: Induction of TCR gene rearrangements in uncommitted stem cells by a subset of IL-7 producing, MHC class-II-expressing thymic stromal cells. Immunity 6:351-360, 1997.
Kelley KW, Brief S, Westly HJ, Novakofski J, Bechtel PJ, Simon J, Walker EB: GH3 pituitary adenoma cells can reverse thymic aging in rats. Proc Natl Acad Sci USA 83:5663-5667, 1986.
Li YM, Brunke DL, Dantzer R, Kelley KW: Pituitary epithelial cell implants reverse the accumulation of CD42CD82 lymphocytes in thymus glands of aged rats. Endocrinology 130:2703-2709, 1992.
Binz K, Joller P, Froesch P, Binz H, Zapf J, Froesch ER: Repopulation of the atrophied thymus in diabetic rats by insulinlike growth factor I. Proc Natl Acad Sci USA 87:3690-3694, 1990.
Marchetti B, Guarcello V, Morale MC, Bartoloni G, Raiti F, Palumbo G, Jr, Farinella Z, Cordaro S, Scapagnini U: Luteinizing hormone-releasing hormone (LHRH) agonist restoration of ageassociated decline of thymus weight, thymic LHRH receptors, and thymocyte proliferative capacity. Endocrinology 125:1037-1045, 1989.
Kendall MD, Fitzpatrick FT, Greenstein BD, Khoylou F, Safieh B, Hamblin A: Reversal of ageing changes in the thymus of rats by chemical or surgical castration. Cell Tissue Res 261:555-564, 1990.
Fitzpatrick FT, Kendall MD, Wheeler MJ, Adcock IM, Greenstein BD: Reappearance of thymus of ageing rats after orchidectomy. J Endocrinol 106:R17-9, 1985.
Aspinall R, Andrew D: Thymic atrophy in the mouse is a soluble problem of the thymic microenvironment. Vaccine 18:1629-1637, 2000.
Bui T, Faltynek C, Ho RJ: Differential disposition of soluble and liposome-formulated human recombinant interleukin-7: Effects on blood lymphocyte population in guinea pigs. Pharm Res 11:633-641, 1994.
Tanchot C, Rocha B: Peripheral selection of T cell repertoires: The role of continuous thymus output. J Exp Med 186:1099-1106, 1997.
Berzins SP, Boyd RL, Miller JF: The role of the thymus and recent thymic migrants in the maintenance of the adult peripheral lymphocyte pool. J Exp Med 187:1839-1848, 1998.
Berzins SP, Godfrey DI, Miller JF, Boyd RL: A central role for thymic emigrants in peripheral T cell homeostasis. Proc Natl Acad Sci USA 96:9787-9791, 1999.
Thoman ML: Effects of the aged microenvironment on CD4+ T cell maturation. Mech Ageing Dev 96:75-88, 1997