Skip to main content
SpringerLink
Log in

Cell death in the rat thymus: A minireview

  • Published:
Apoptosis Aims and scope Submit manuscript

Abstract

During the last decades, the literature has clearly established the fundamental role of the thymus in the development of an effective immune system. During thymocyte development and maturation, potentially autoreactive thymocytes are eliminated by a process known as apoptosis or programmed cell death responsible for the negative selection occurring within the thymus. This process is in sharp contrast to other types of cell death referred to as necrosis. Actually, three different types of cell death have been recently observed morphologically in the rat thymus, i.e. necrosis, apoptosis and clustered cell death. Moreover, among the numerous factors influencing thymocyte cell death, particular attention has been paid to hormones, chemicals, biological compounds and physical agents that may influence the type and/or the extent of cell death. Finally, a brief overview has been devoted to the contribution of mitochondria, nitric oxide, glutathione and intracellular levels of cations in addition to the activity of genes as cdk2, p53, Fas and members' of the Bcl2 family in modulating rat thymus cell death.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Miller JF. Uncovering thymus function. Perspect Biol Med 1996; 39: 338-352.

    Google Scholar 

  2. Miller JF. Immunological function of the thymus. Lancet 1961; 2: 748.

    Google Scholar 

  3. Claman HN, Chaperon EA, Triplett RF. Thymus marrow cell combinations. Synergism in antibody production. Proc Soc Exp Biol Med 1966; 122: 1167-1171.

    Google Scholar 

  4. Miller JF, Mitchell GF. The thymus and the precursors of antigen reactive cells. Nature 1967; 216: 659-663.

    Google Scholar 

  5. Mitchell GF, Miller JF. Immunological activity of thymus and thoracic duct lymphocytes. Proc Natl Acad Sci USA 1968; 59: 296-303.

    Google Scholar 

  6. Miller JF, Basten A, Sprent J, Cheers C. Interaction between lymphocytes in immune responses. Cell Immunol 197; 2: 469-495.

  7. Miller JF, Sprent J. Cell to cell interaction in the immune response. VI. Contribution of thymus derived cells and antibody forming cell precursors to immunological memory. J Exp Med 1971; 134: 66-82.

    Google Scholar 

  8. Miller JF. Cellular basis of immune responses. Folia Allergol Roma 1970; 17: 381-382.

    Google Scholar 

  9. Scollay R, Shortman K. Thymocyte subpopulations:Anexperimental review, including flow cytometric cross correlations between the major murine thymocyte markers. Thymus 1983; 5: 245-295.

    Google Scholar 

  10. Quaglino D Jr, Capri M, Bergamini G, Euclidi E, Zecca L, Franceschi C, Pasquali-Ronchetti I. Age dependent remodeling of rat thymus. Morphological and cytofluorimetric analysis from birth up to one year of age. Eur J Cell Biol 1998, 76: 156-166.

    Google Scholar 

  11. Capri M, Quaglino D Jr, Verzella G, et al. A cytofluorimetric study of T lymphocyte subsets in rat lymphoid tissues (thymus, lymph nodes) and peripheral blood: A continuous remodelling during the first year of life. Exp Gerontol 2000; 35: 613-625.

    Google Scholar 

  12. Thoman ML. The pattern of T lymphocyte differentiation is altered during thymic involution. Mech Ageing Dev 1995; 82: 155-170.

    Google Scholar 

  13. Kay MM, Makinodan T. Immunobiology of aging: Evaluation of current status. Clin Immunol Immunopathol 1976; 6: 394-413.

    Google Scholar 

  14. Segal J, Troen BR, Ingbar SH. Effects of age and sex on certain metabolic functions and mitogenic activity in rat thymocytes. Thymus 1985; 7: 211-220.

    Google Scholar 

  15. Schuurman HJ, Nagelkerken L, DeWeger RA, Rozing J. Age associated involution: Significance of a physiologic process. Thymus 1991; 18: 1-6.

    Google Scholar 

  16. Swat W, Ignatowicz L, von Boehmer H, Kisielow P. Clonal deletion of immature CD4+8+ thymocytes in suspension culture by extrathymic antigen presenting cells. Nature 1991; 351: 150-153.

    Google Scholar 

  17. Kishimoto H, Surh CD, Sprent J. Upregulation of surface markers on dying thymocytes. J Exp Med 1995; 181: 649-655.

    Google Scholar 

  18. Fesus L, Davies PJ, Piacentini M. Apoptosis: Molecular mechanisms in programmed cell death. Eur J Cell Biol 1991; 56: 170-177.

    Google Scholar 

  19. Feldmann G. Apoptosis. Ann Pharm Fr 1999; 57: 291-308.

    Google Scholar 

  20. Sprent J, Kishimoto H, Cai Z, et al. The thymus and T cell death. Adv Exp Med Biol 1996; 406: 191-198.

    Google Scholar 

  21. Fadeel B, Zhivotovsky B, Orrenius S. All along the watchtower: On the regulation of apoptosis regulators. FASEB J 1999; 13: 1647-1657.

    Google Scholar 

  22. Fiers W, Beyaert R, Declercq W, Vandenabeele P. More than one way to die: Apoptosis, necrosis and reactive oxygen damage. Oncogene 1999; 18: 7719-7730.

    Google Scholar 

  23. Golstein P, Ojcius DM, Young JD. Cell death mechanisms and the immune system. Immunol Rev 1991; 121: 29-65.

    Google Scholar 

  24. Cairns JS, Mainwaring MS, Cacchione RN, Walker JA, McCarthy SA. Regulation of apoptosis in thymocytes. Thymus 1993; 21: 177-193.

    Google Scholar 

  25. Inomata T, Hyodo T, Sakita K, et al. Influence of adrenalectomy on the developing rat thymus during peri-weaning period. Anat Histol Embryol 1993; 22: 296-299.

    Google Scholar 

  26. Sainte Marie G, Peng FS. Atrophy of compartments of rat lymph nodes related to an entry of lethally altered lymphocytes. Cell Tissue Res 1990; 262: 263-271.

    Google Scholar 

  27. Selye H. Thymus and adrenals in the response of the organism to injuries and intoxicants. Br J Exp Pathol 1936; 17: 234-248.

    Google Scholar 

  28. Compton MM, Caron LA, Cidlowski JA. Glucocorticoid action on the immune system. J Steroid Biochem 1987; 27: 201-208.

    Google Scholar 

  29. Munck A, Guyre PM, Holbrook NJ. Physiological functions of glucocorticoids in stress and their relation to pharmacological actions. Endocr Rev 1984; 5: 25-44.

    Google Scholar 

  30. Thomas N, Edwards JL, Bell PA. Studies of the mechanism of glucocorticoid-induced pyknosis in isolated rat thymocytes. J Steroid Biochem 1983, 18: 519-524.

    Google Scholar 

  31. Wyllie AH. Glucocorticoid induced thymocyte apoptosis is associated with endogenous endonuclease activation. Nature 1980; 284: 555-556.

    Google Scholar 

  32. Compton MM, Cidlowski JA. Identification of a glucocorticoid induced nuclease in thymocytes. A potential "lysis gene" product. J Biol Chem 1987; 262: 8288-8292.

    Google Scholar 

  33. Compton MM. A biochemical hallmark of apoptosis: Internucleosomal degradation of the genome. Cancer Metastasis Rev 1992; 11: 105-119.

    Google Scholar 

  34. Arends MJ, Wyllie AH. Apoptosis: Mechanisms and roles in pathology. Int Rev Exp Pathol 1991; 32: 223-254.

    Google Scholar 

  35. Cohen JJ. Programmed cell death in the immune system. Adv Immunol 1991; 50: 55-85.

    Google Scholar 

  36. Wyllie AH, Kerr JF, Currie AR. Cell death: The significance of apoptosis. Int Rev Cytol 1980; 68: 251-306.

    Google Scholar 

  37. Thomas N, Bell PA. Glucocorticoid induced cell size changes and nuclear fragility in rat thymocytes. Mol Cell Endocrinol 1981; 22: 71-84.

    Google Scholar 

  38. Cohen JJ, Duke RC. Glucocorticoid activation of a calcium dependent endonuclease in thymocyte nuclei leads to cell death. J Immunol 1984; 132: 38-42.

    Google Scholar 

  39. Sellins KS, Cohen JJ. Gene induction by gamma irradiation leads to DNA fragmentation in lymphocytes. J Immunol 1987; 139: 3199-3206.

    Google Scholar 

  40. Wyllie AH, Morris RG, Smith AL, Dunlop D. Chromatin cleavage in apoptosis: Association with condensed chromatin morphology and dependence on macromolecular synthesis. J Pathol 1984; 142: 67-77.

    Google Scholar 

  41. Smith CA, Williams GT, Kingston R, Jenkinson EJ, Owen JJ. Antibodies to CD3/T cell receptor complex induce death by apoptosis in immature T cells in thymic cultures. Nature 1989; 337: 181-184.

    Google Scholar 

  42. Kerr JF, Wyllie AH, Currie AR. Apoptosis: A basic biological phenomenon with wide ranging implications in tissue kinetics. Br J Cancer 1972; 26: 239-257.

    Google Scholar 

  43. McConkey DJ, Hartzell P, Nicotera P, Orrenius S. Calcium activated DNA fragmentation kills immature thymocytes. FASEB J 1989; 3: 1843-1849.

    Google Scholar 

  44. Nakamura M, Yagi H, Kayaba S, et al. Most thymocytes die in the absence of DNA fragmentation. Arch Histol Cytol 1995; 58: 249-256.

    Google Scholar 

  45. Cohen GM, Sun XM, Snowden RT, Dinsdale D, Skilleter DN. Key morphological features of apoptosis may occur in the absence of internucleosomal DNA fragmentation. Biochem J 1992; 286: 331-334.

    Google Scholar 

  46. Mann CL, Hughes FM Jr, Cidlowski JA. Delineation of the signaling pathways involved in glucocorticoid induced and spontaneous apoptosis of rat thymocytes. Endocrinology 2000; 141: 528-538.

    Google Scholar 

  47. Stuart MC, Damoiseaux JG, Frederik PM, Arends JW, Reutelingsperger CP. Surface exposure of phosphatidylserine during apoptosis of rat thymocytes precedes nuclear changes. Eur J Cell Biol 1998; 76: 77-83.

    Google Scholar 

  48. Oldenburg NB, Evans Storms RB, Cidlowski JA. In vivo resistance to glucocorticoid induced apoptosis in rat thymocytes with normal steroid receptor function in vitro. Endocrinology 1997; 138: 810-818.

    Google Scholar 

  49. Darzynkiewicz Z, Bruno S, Del Bino G, et al. Features of apoptotic cells measured by flow cytometry. Cytometry 1992; 13: 795-808.

    Google Scholar 

  50. Bruno S, Lassota P, Giaretti W, Darzynkiewicz Z. Apoptosis of rat thymocytes triggered by prednisolone, camptothecin, or teniposide is selective to G0 cells and is prevented by inhibitors of proteases. Oncol Res 1992; 4: 29-35.

    Google Scholar 

  51. Berger NA, Berger SJ, Sudar DC, Distelhorst CW. Role of nicotinamide adenine dinucleotide and adenosine triphosphate in glucocorticoid induced cytotoxicity in susceptible lymphoid cells. J Clin Invest 1987; 79: 1558-1563.

    Google Scholar 

  52. Buttke TM, Sandstrom PA. Oxidative stress as a mediator of apoptosis. Immunol Today 1994; 15: 7-10.

    Google Scholar 

  53. Slater AF, Stefan C, Nobel I, van den Dobbelsteen DJ, Orrenius S. Signalling mechanisms and oxidative stress in apoptosis. Toxicol Lett 1995; 83: 149-153.

    Google Scholar 

  54. Sainz RM, Mayo JC, Uria H, et al. The pineal neurohormone melatonin prevents in vivo and in vitro apoptosis in thymocytes. J Pineal Res 1995; 19: 178-188.

    Google Scholar 

  55. Sakamoto T, Repasky WT, Uchida K, Hirata A, Hirata F. Modulation of cell death pathways to apoptosis and necrosis of H2O2 treated rat thymocytes by lipocortin I. Biochem Biophys Res Commun 1996; 220: 643-647.

    Google Scholar 

  56. Shaposhnikova VV, Egorova MV, Levitman MKh, Kudriavtsev AA, Sukharev VI, Korystov IuK. Proliferation and death of thymocytes caused by phospholipase A2 activator melittin. Izv Akad Nauk Ser Biol 1998; 2: 225-229.

    Google Scholar 

  57. French LE, Sappino AP, Tschopp J, Schifferli JA. Clusterin gene expression in the rat thymus is not modulated by dexamethasone treatment. Immunology 1994; 82: 328-331.

    Google Scholar 

  58. Barke RA, Roy S, Chapin RB, Charboneau R. The role of programmed cell death (apoptosis) in thymic involution following sepsis. Arch Surg 1994; 129: 1256-1262.

    Google Scholar 

  59. Bustamante J, Dock L, Vahter M, Fowler B, Orrenius S. The semiconductor elements arsenic and indium induce apoptosis in rat thymocytes. Toxicology 1997; 118: 129-136.

    Google Scholar 

  60. Schuurman HJ, Kuper CF, Vos JG. Histopathology of the immune system as a tool to assess immunotoxicity. Toxicology 1994; 86: 187-212.

    Google Scholar 

  61. Concordet JP, Ferry A. Physiological programmed cell death in thymocytes is induced by physical stress (exercise). Am J Physiol 1993; 265: C626-C629.

    Google Scholar 

  62. Capri M, Quaglino D Jr, Zecca L, Pasquali Ronchetti I, Franceschi C. Thymus as possible target of long exposure to 50 Hz sinusoidal electric and magnetic fields. In: Bersani F, ed. Electricity and magnetism in biology and medicine. New York: Kluwer Academic/Plenum Publisher, 1999: 195-198.

    Google Scholar 

  63. Cadossi R, Bersani F, Cossarizza A, et al. Lymphocytes and low frequency electromagnetic fields. FASEB J 1992; 6: 2667-2674.

    Google Scholar 

  64. Cossarizza A, Monti D, Sola P, et al. DNA repair after gamma irradiation in lymphocytes exposed to low frequency pulsed electromagnetic fields. Radiat Res 1989; 118: 161-168.

    Google Scholar 

  65. Quaglino D Jr, Capri M, Pasquali Ronchetti I. Modulation of cell death in the rat thymus. Light and electron microscopic investigations. Ann N Y Acad Sci USA 2000; 926: 79-82.

    Google Scholar 

  66. Mahmoud I, Salman SS, al Khateeb A. Continuous darkness and continuous light induce structural changes in the rat thymus. J Anat 1994; 185: 143-149.

    Google Scholar 

  67. Vollmar AM, Colbatzky F, Schulz R. Increased production of atrial natriuretic peptide in the rat thymus after irradiation. Immunopharmacology 1993; 26: 65-72.

    Google Scholar 

  68. Zhivotovsky B, Nicotera P, Bellomo G, Hanson K, Orrenius S. Ca2+ and endonuclease activation in radiation induced lymphoid cell death. Exp Cell Res 1993; 207: 163-170.

    Google Scholar 

  69. Grassilli E, Desiderio MA, Bellesia E, Salomoni P, Benatti F, Franceschi C. Is polyamine decrease a common feature of apoptosis? Evidence from gamma rays and heat shock induced cell death. Biochem Biophys Res Commun 1995; 216: 708-714.

    Google Scholar 

  70. Bossy Wetzel E, Green DR. Apoptosis: Checkpoint at the mitochondrial frontier. Mutat Res 1999; 434: 243-251.

    Google Scholar 

  71. Mignotte B, Vayssiere JL. Mitochondria and apoptosis. Eur J Biochem 1998; 252: 1-15.

    Google Scholar 

  72. Kroemer G. Mitochondrial control of apoptosis: An overview. Biochem Soc Symp 1999; 66: 1-15.

    Google Scholar 

  73. Wallace KB, Eells JT, Madeira VM, Cortopassi G, Jones DP. Mitochondria mediated cell injury. Symposium overview. Fundam Appl Toxicol 1997; 38: 23-37.

    Google Scholar 

  74. Cossarizza A, Kalashnikova G, Grassilli E, et al. Mitochondrial modifications during rat thymocyte apoptosis: A study at the single cell level. Exp Cell Res 1994; 214: 323-330.

    Google Scholar 

  75. Salvioli S, Barbi C, Dobrucki, et al. Opposite role of changes in mitochondrial membrane potential in different apoptotic processes. FEBS Lett 2000; 469: 186-190.

    Google Scholar 

  76. Bustamante J, Bersier G, Romero M, Badin RA, Boveris A. Nitric oxide production and mitochondrial dysfunction during rat thymocyte apoptosis. Arch Biochem Biophys 2000; 376: 239-247.

    Google Scholar 

  77. Lin YS, Kuo HL, Kuo CF, Wang ST, Yang BC, Chen HI. Antioxidant administration inhibits exercise induced thymocyte apoptosis in rats. Med Sci Sports Exerc 1999; 31: 1594-1598.

    Google Scholar 

  78. Kozlowska M, Smolenski RT, Makarewicz W, Hoffmann C, Jastorff B, Swierczynski J. ATP depletion, purine riboside triphosphate accumulation and rat thymocyte death induced by purine riboside. Toxicol Lett 1999; 104: 171-181.

    Google Scholar 

  79. Bustamante J, Slater AF, Orrenius S. Antioxidant inhibition of thymocyte apoptosis by dihydrolipoic acid. Free Radic Biol Med 1995; 19: 339-347.

    Google Scholar 

  80. McConkey DJ. The role of calcium in the regulation of apoptosis. Scanning Microsc 1996; 10: 777-794.

    Google Scholar 

  81. Nicotera P, Zhivotovsky B, Orrenius S. Nuclear calcium transport and the role of calcium in apoptosis. Cell Calcium 1994; 16: 279-288.

    Google Scholar 

  82. Shaposhnikova VV, Dobrovinskaya OR, Gukovskaya AS, Trepakova ES, Korystov YN. On the role of intracellular concentration of Ca2+ and H+ in thymocyte death after irradiation. FEBS Lett 1993; 324: 274-276.

    Google Scholar 

  83. Story MD, Stephens LC, Tomasovic SP, Meyn RE. A role for calcium in regulating apoptosis in rat thymocytes irradiated in vitro. Int J Radiat Biol 1992; 61: 243-251.

    Google Scholar 

  84. Barbieri D, Troiano L, Grassilli E, et al. Inhibition of apoptosis by zinc: A reappraisal. Biochem Biophys Res Commun 1992; 187: 1256-1261.

    Google Scholar 

  85. McCabe MJ Jr, Jiang SA, Orrenius S. Chelation of intracellular zinc triggers apoptosis in mature thymocytes. Lab Invest 1993; 69: 101-110.

    Google Scholar 

  86. Samali A, Zhivotovsky B, Jones DP, Orrenius S. Detection of pro caspase 3 in cytosol and mitochondria of various tissues. FEBS Lett 1998; 431: 167-169.

    Google Scholar 

  87. Earnshaw WC, Martins LM, Kaufmann SH. Mammalian caspases: Structure, activation, substrates, and functions during apoptosis. Annu Rev Biochem 1999; 68: 383-424.

    Google Scholar 

  88. Robertson JD, Orrenius S, Zhivotovsky B. Review: Nuclear events in apoptosis. J Struct Biol 2000; 129: 346-358.

    Google Scholar 

  89. Hughes FM Jr, Evans Storms RB, Cidlowski JA. Evidence that non caspase proteases are required for chromatin degradation during apoptosis. Cell Death Differ 1998; 5: 1017-1027.

    Google Scholar 

  90. Arends MJ, Morris RG, Wyllie AH. Apoptosis. The role of the endonuclease. Am J Pathol 1990; 136: 593-608.

    Google Scholar 

  91. Chow SC, Weis M, Kass GE, Holmstrom TH, Eriksson JE, Orrenius S. Involvement of multiple proteases during Fas mediated apoptosis in T lymphocytes. FEBS Lett. 1995; 364: 134-138.

    Google Scholar 

  92. Kass GE, Eriksson JE, Weis M, Orrenius S, Chow SC. Chromatin condensation during apoptosis requires ATP. Biochem J 1996; 318: 749-752.

    Google Scholar 

  93. Hakem A, Sasaki T, Kozieradzki I, Penninger JM. The cyclin dependent kinase Cdk2 regulates thymocyte apoptosis. J Exp Med 1999; 189: 957-968.

    Google Scholar 

  94. Gil Gomez G, Berns A, Brady HJ. A link between cell cycle and cell death: Bax and Bcl 2 modulate Cdk2 activation during thymocyte apoptosis. EMBO J 1998; 17: 7209-7218.

    Google Scholar 

  95. Norbury C, MacFarlane M, Fearnhead H, Cohen GM. Cdc2 activation is not required for thymocyte apoptosis. Biochem Biophys Res Commun 1994; 202: 1400-1406.

    Google Scholar 

  96. Brady HJ, Gil Gomez G. The cell cycle and apoptosis. Results Probl Cell Differ 1999; 23: 127-144.

    Google Scholar 

  97. Grassilli E, Carcereri de Prati A, Monti D, et al. Studies of the relationship between cell proliferation and cell death. II. Early gene expression during concanavalinAinduced proliferation or dexamethasone induced apoptosis of rat thymocytes. Biochem Biophys Res Commun 1992; 188: 1261-1266.

    Google Scholar 

  98. Beneke R, Geisen C, Zevnik B, et al.. DNA excision repair and DNA damage induced apoptosis are linked to Poly(ADP ribosyl)ation but have different requirements for p53. Mol Cell Biol 2000; 20: 6695-6703.

    Google Scholar 

  99. Kapasi AA, Singhal PC. Aging splenocyte and thymocyte apoptosis is associated with enhanced expression of p53, bax, and caspase 3. Mol Cell Biol Res Commun 1999; 1: 78-81.

    Google Scholar 

  100. MacFarlane M, Jones NA, Dive C, Cohen GM. DNA damaging agents induce both p53 dependent and p53 independent apoptosis in immature thymocytes. Mol Pharmacol 1996; 50: 900-911.

    Google Scholar 

  101. Rathmell JC, Thompson CB. The central effectors of cell death in the immune system. Annu Rev Immunol 1999; 17: 781-828.

    Google Scholar 

  102. King KL, Cidlowski JA. Cell cycle and apoptosis: Common pathways to life and death. J Cell Biochem 1995; 58: 175-180.

    Google Scholar 

  103. Motyl T. Regulation of apoptosis: Involvement of Bcl 2 related proteins. Reprod Nutr Dev 1999; 39: 49-59.

    Google Scholar 

  104. Tsujimoto Y, Finger LR, Yunis J, Nowell PC, Croce CM. Cloning of the chromosome breakpoint of neoplastic B cells with the t(14;18) chromosome translocation. Science 984; 226: 1097-1099.

  105. Marin MC, Hsu B, Meyn RE, Donehower LA, el Naggar AK, McDonnell TJ. Evidence that p53 and bcl 2 are regulators of a common cell death pathway important for in vivo lymphomagenesis. Oncogene 1994; 9: 3107-1312.

    Google Scholar 

  106. Boise LH, Gonzalez Garcia M, Postema CE, et al. Bcl x, a bcl 2 related gene that functions as a dominant regulator of apoptotic cell death. Cell 1993; 74: 597-608.

    Google Scholar 

  107. Kozopas KM, Yang T, Buchan HL, Zhou P, Craig RW. MCL1, a gene expressed in programmed myeloid cell differentiation, has sequence similarity to BCL2. Proc Natl Acad Sci USA 1993; 90: 3516-3520.

    Google Scholar 

  108. Oltvai ZN, Milliman CL, Korsmeyer SJ. Bcl 2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell 1993; 74: 609-619.

    Google Scholar 

  109. Yang E, Zha J, Jockel J, Boise LH, Thompson CB, Korsmeyer SJ. Bad, a heterodimeric partner for Bcl XL and Bcl 2, displaces Bax and promotes cell death. Cell 1995; 80: 285-291.

    Google Scholar 

  110. Kroemer G. The proto oncogene Bcl 2 and its role in regulating apoptosis Nat Med 1997; 3: 614-620.

    Google Scholar 

  111. Adams JM, Cory S. The Bcl 2 protein family: Arbiters of cell survival. Science 998; 281: 1322-1326.

  112. Reed JC. Bcl 2 family proteins. Oncogene 1998; 17: 3225-3236.

    Google Scholar 

  113. Hockenbery DM, Oltvai ZN, Yin XM, Milliman CL, Korsmeyer SJ. Bcl 2 functions in an antioxidant pathway to prevent apoptosis. Cell 1993; 75: 241-251.

    Google Scholar 

  114. Voehringer DW, McConkey DJ, McDonnell TJ, Brisbay S, Meyn RE. Bcl 2 expression causes redistribution of glutathione to the nucleus. Proc Natl Acad Sci USA 1998; 95: 2956-2960.

    Google Scholar 

  115. Haldar S, Basu A, Croce CM. Bcl2 is the guardian of microtubule integrity. Cancer Res 1997; 57: 229-233.

    Google Scholar 

  116. Akao Y, Otsuki Y, Kataoka S, Ito Y, Tsujimoto Y. Multiple subcellular localization of bcl 2: Detection in nuclear outer membrane, endoplasmic reticulum membrane, and mitochondrial membranes. Cancer Res 1994; 54: 2468-2471.

    Google Scholar 

  117. Sentman CL, Shutter JR, Hockenbery D, Kanagawa O, Korsmeyer SJ. Bcl 2 inhibits multiple forms of apoptosis but not negative selection in thymocytes. Cell 1991; 67: 879-888.

    Google Scholar 

  118. Sakamoto T, Repasky WT, Chen J, Hirata A, Hirata F. Down regulation of bcl xs gene expression in rat thymocytes by dexamethasone. Biochem Biophys Res Commun 1995; 215: 511-516.

    Google Scholar 

  119. Krajewski S, Bodrug S, Gascoyne R, Berean K, Krajewska M, Reed JC. Immunohistochemical analysis of Mcl 1 and Bcl 2 proteins in normal and neoplastic lymph nodes. Am J Pathol 1994; 145: 515-525.

    Google Scholar 

  120. Gonzalez Garcia M, Perez Ballestero R, Ding L, et al. Bcl XL is the major bcl x mRNA form expressed during murine development and its product localizes to mitochondria. Development 1994; 120: 3033-3042.

    Google Scholar 

  121. Williams O, Norton T, Halligey M, Kioussis D, Brady HJM. The action of Bax and bcl 2 on T cell selection. J Exp Med 1998; 188: 1125-1133.

    Google Scholar 

  122. Hsu YT, Wolter KG, Youle RJ. Cytosol to membrane redistribution of Bax and Bcl X(L) during apoptosis. Proc Natl Acad Sci USA 1997; 94: 3668-3672.

    Google Scholar 

  123. Dietrich JB. Apoptosis and anti apoptosis genes in the Bcl 2 family. Arch Physiol Biochem 1997; 105: 125-135.

    Google Scholar 

  124. St. Clair EG, Anderson SJ, Oltvai ZN. Bcl 2 counters apoptosis by Bax heterodimerization dependent and independent mechanisms in the T cell lineage. J Biol Chem 1997; 272: 29347-29355.

    Google Scholar 

  125. Takayama S, Sato T, Krajewski S, et al. Cloning and functional analysis of BAG 1: A novel Bcl 2 binding protein with anti cell death activity. Cell 1995; 80: 279-284.

    Google Scholar 

  126. Trauth BC, Klas C, Peters AM, et al. Monoclonal antibody mediated tumor regression by induction of apoptosis. Science 1989; 245: 301-305.

    Google Scholar 

  127. Tartaglia LA, Ayres TM, Wong GH, Goeddel DV. A novel domain within the 55 kd TNF receptor signals cell death. Cell 1993; 74: 845-853.

    Google Scholar 

  128. Varadhachary AS, Salgame P. CD95 mediated T cell apoptosis and its relevance to immune deviation. Oncogene 1998; 17: 3271-3276.

    Google Scholar 

  129. Peter ME, Krammer PH. Mechanisms of CD95 (APO 1/Fas) mediated apoptosis. Curr Opin Immunol 1998; 10: 545-551.

    Google Scholar 

  130. Wang GJ, Cai L. Relatively low dose cyclophosphamide is likely to induce apoptotic cell death in rat thymus through Fas/Fas ligand pathway. Mutat Res 1999; 427: 125-133.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biomedical Sciences—General Pathology, University of Modena and Reggio Emilia, Modena, Italy

    D. Quaglino

  2. Department of Biomedical Sciences—General Pathology, University of Modena and Reggio Emilia, Modena, Italy

    I. Pasquali Ronchetti

Authors
  1. D. Quaglino
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. I. Pasquali Ronchetti
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Quaglino, D., Ronchetti, I.P. Cell death in the rat thymus: A minireview. Apoptosis 6, 389–401 (2001). https://doi.org/10.1023/A:1011394304691

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1011394304691

Search

Navigation