Is thymus redundant after adulthood?

Immunology Letters

Volumn 91, Issue 2-3, 2004, Pages 79-86

  Shanker, Anil ^a,b  

^a CNRS   (France)

^b SAIC FREDERICK INC   (United States)

Author keywords

Adult thymus function; Stress; T cell reconstitution; Thymic atrophy; Thymic import and export; Tumour

Indexed keywords

AGING; CANCER; GRAFT VERSUS HOST REACTION; HEMATOPOIETIC STEM CELL TRANSPLANTATION; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IMMUNE SYSTEM; INFECTION; INVOLUTION; NONHUMAN; PREGNANCY; PRIORITY JOURNAL; REVIEW; SEASON; STRESS; THYMUS; THYMUS ATROPHY; TUMOR GROWTH;

AGING; ANIMALS; ATROPHY; HUMANS; NEOPLASMS; STRESS; T-LYMPHOCYTES; THYMUS GLAND;

EID: 1542332647     PISSN: 01652478     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.imlet.2003.12.012     Document Type: Review

References (116)

1. Miller J.F.A.P. Immunological function of the thymus. Lancet. 2:1961;748-749.
2. Martinez C., Kersey J., Papermaster B.W., Good R.A. Skin homograft survival in thymectomized mice. Proc. Soc. Exp. Biol. Med. 109:1962;193-196.
3. Arnason B.G., Jankovic B.D., Waksman B.H. Effect of thymectomy on "delayed" hypersensitive reactions. Nature. 194:1962;99-100.
4. Derbinski J., Schulte A., Kyewski B., Klein L. Promiscuous gene expression in medullary thymic epithelial cells mirrors the peripheral self. Nat. Immunol. 2:2001;1032-1039.
5. Rocha B., Freitas A.A., Coutinho A.A. Population dynamics of T lymphocytes. Renewal rate and expansion in the peripheral lymphoid organs. J. Immunol. 131:1983;2158-2164.
6. Rocha B., Von Boehmer H. Peripheral selection of the T cell repertoire. Science. 251:1991;1225-1228.
7. Mackall C.L., Gress R.E. Thymic aging and T-cell regeneration. Immunol. Rev. 160:1997;91-102.
8. Hammar J.A. The new views as to the morphology of the thymus gland and their bearing on the problem of the function of the thymus. Endocrinology. 5:1921;543-573. 731-760.
9. Boyd E. Growth of the thymus. Its relation to status thymico-lymphaticus and thymic symptoms. Am. J. Dis. Child. 33:1927;867-879.
10. Greenwood M., Woods H.M. "Status thymico-lymphaticus" considered in the light of recent work on the thymus. J. Hyg. 26:1927;305-326.
11. Steinmann GG. Changes in the human thymus during aging. In: Muller-Hermelink HK, editor. The human thymus: histopathology and pathology. New York: Springer-Verlag, 1986. p. 43-88.
12. Kendall M.D. Functional anatomy of the thymic microenvironment. J. Anat. 177:1991;1-29.
13. Simpson J.G., Gray E.S., Beck J.S. Age involution in the normal human adult thymus. Clin. Exp. Immunol. 19:1975;261-265.
14. Moore A.V., Korobkin M., Olanow W., Heaston D.K., Ram P.C., Dunnick N.K.et al. Age-related changes in the thymus gland: CT-pathologic correlation. AJR Am. J. Roentgenol. 141:1983;241-246.
15. Francis I.R., Glazer G.M., Bookstein F.L., Gross B.H. The thymus: reexamination of age-related changes in size and shape. AJR Am. J. Roentgenol. 145:1985;249-254.
16. Boday B., Bodey B. Jr., Siegel S.E., Kaiser H.E. Involution of the mammalian thymus, one of the leading regulators of aging. In Vivo. 11:1997;421-440.
17. Seddon B., Mason D. The third function of the thymus. Immunol. Today. 21:2000;95-99.
18. Baruah B.D. Cellular reactions following tumor growth with special reference to plasma-cellular response. Cancer Res. 20:1960;1184-1190.
19. Tanaka K., Koga Y., Taniguchi K., Nomoto K. T cell recruitment from the thymus to spleen in tumor-bearing mice. Cancer Res. 47:1987;2136-2140.
20. Edwards A.J., Sumner M.R., Rowland G.F., Hurd C.M. Changes in lymphoreticular tissue during growth of a murine adenocarcinoma. J. Natl. Cancer Inst. 47:1971;313-338.
21. Aherne W.A., Zaitoun A.M., Louder I., Hull D.L. Cytokinetic changes in the thymus of tumor bearing and of dexamethasone treated mice. Cell Tiss. Kinet. 13:1980;485-489.
22. Lee M.Y., Rosse C. Depletion of lymphocyte subpopulations in primary and secondary lymphoid organs of mice by a transplanted granulocytosis-inducing mammary carcinoma. Cancer Res. 42:1982;1255-1260.
23. Thomas E., Smith D.C., Lee M.Y., Rosse C. Induction of granulocytic hyperplasia, thymic atrophy, and hypercalcemia by a selected subpopulation of a murine mammary adenocarcinoma. Cancer Res. 45:1985;5840-5844.
24. Fu Y.-X., Paul R.D., Wang Y., Lopez D.M. Thymic involution and thymocyte phenotypic alterations induced by murine mammary adenocarcinomas. J. Immunol. 143:1989;4300-4307.
25. Gallo F., Morale M.C., Sambataro D., Farinella Z., Scapagnani U., Marchetti B. Immune system response during development and progression of carcinogen-induced rat mammary tumors: prevention of tumor growth and restoration of immune system responsiveness by thymopentin. Breast Cancer Res. Treat. 27:1993;221-226.
26. Efskind L., Godal T., Grude T., Marton P.F., Mossige J., Hoglo S. Progressive atrophy of the thymus in mice carrying Lewis lung carcinoma grafts. Cancer Immunother. 3:1978;207-209.
27. Simpson R.M., Zhao T.M., Hubbard B.S., Sawasdikosol S., Kindt T.J. Experimental acute adult T cell leukemia lymphoma is associated with thymic atrophy in human T cell leukemia virus type I infection. Lab. Invest. 74:1996;696-710.
28. Hanaoka M., Sasaki M., Matsumoto H., Tankawa H., Yamabe H., Tomimoto K. et al. Adult T cell leukemia histological classification and characteristics. Acta Pathol. Jpn. 29:1979;723-738.
29. Morimura T., Hattori M., Ohashi K., Sugimoto C., Onuma M. Immunomodulation of peripheral T cells in chickens infected with Marek's disease virus: involvement in immunosuppression. J. Gen. Virol. 76:1995;2979-2985.
30. Morimura T., Ohashi K., Kon Y., Hattori M., Sugimoto C., Onuma M. Apoptosis and CD8-down-regulation in the thymus of chickens infected with Marek's disease virus. Arch. Virol. 141:1996;2243-2249.
31. Shanker A., Singh S.M., Sodhi A. Ascitic growth of a transplantable T-cell lymphoma of spontaneous origin induces thymic involution. I. Alterations in the CD4/CD8 distribution in thymocytes. Tumor Biol. 21:2000;288-298.
32. Shanker A., Singh S.M., Sodhi A. Ascitic growth of a transplantable T-cell lymphoma of spontaneous origin induces thymic involution. II. Induction of apoptosis in thymocytes. Tumor Biol. 21:2000;315-327.
33. Shanker A., Singh S.M. Characterisation of factors inducing apoptosis in thymocytes of mice bearing a transplantable T-cell lymphoma of spontaneous origin. Neoplasma. 47:2000;90-95.
34. Roy R., Singh S.M., Shanker A., Sodhi A. Mechanism of thymocyte apoptosis induced by serum of tumor-bearing host: the molecular events involved and their inhibition by thymosin α-1. Int. J. Immunopharmacol. 22:2000;309-321.
35. Ehrke M.J., Verstovsek S., Krawezyk C.M., Ujhazy P., Zaleskis G., Maccubbin D.L.et al. Cyclophosphamide plus tumor necrosis factor a chemoimmunotherapy cured mice: life-long immunity and rejection of re-implanted primary lymphoma. Int. J. Cancer. 63:1995;463-471.
36. Ehrke M.J., Verstovsek S., Pocchiari S.K., Krawczyk C.M., Ujhazy P., Zaleskis G.et al. Thymic anti-tumor effectors in mice cured of lymphoma by cyclophosphamide plus tumor necrosis factor a therapy: phenotypic and functional characterization up to 20 months after initial tumor inoculation. Int. J. Cancer. 76:1998;579-586.
37. Krawezyk C.M., Verstovsek S., Ujhazy P., Maccubbin D., Ehrke M.J. Protective specific immunity induced by cyclophosphamide plus tumor necrosis factor a combination treatment of EL4-lymphoma-bearing C57BL/6 mice. Cancer Immunol. Immunother. 40:1995;347-357.
38. Gregoire C. Thymus and immunity. I. Early thymus research. Eur. J. Cancer Clin. Oncol. 24:1988;1249-1255.
39. Clarke A.G., Kendall M.D. The thymus in the mouse changes its activity during pregnancy: a study of the microenvironment. J. Anat. 197:2000;393-411.
40. Sosnovskii A.S., Kozlov A.V. Increased lipid peroxidation in the rat hypothalamus after short-term emotional stress. Biull. Eksp. Biol. Med. 113:1992;486-488.
41. Rijshinghani A., Bhatia S.K., Kantamneni L., Schlueter A., Waldschmidt T.J. Estrogen inhibits fetal thymocyte development in vitro. Am. J. Reprod. Immunol. 37:1997;384-390.
42. Dominguez-Gerpe L., Rey-Mendez M. Time course of the murine lymphoid tissue involution during and following stress exposure. Life Sci. 61:1997;1019-1027.
43. Xu Y.X., Wichmann M.W., Ayala A., Cioffi W.G., Chaudry I.H. Trauma-haemorrhage induces increased thymic apoptosis while decreasing IL-3 release and increasing GM-CSF. J. Surg. Res. 68:1997;24-30.
44. Seyle H. Thymus and adrenals in the response of the organism to injuries and intoxication. Br. J. Exp. Pathol. 17:1936;234-240.
45. Ward P., Kendall M.D. Morphological changes in the thymus of young and adult red-billed queleas Quelea quelea (aves). Philos. Trans. R. Soc. London B: Biol. Sci. 273:1975;55-64.
46. Cooper E.L., Wright R.K., Klempau A.E., Smith C.T. Hibernation alters the frog's immune system. Cryobiology. 29:1992;616-631.
47. Galletti G., Cavallari A. The thymus of marmots: spontaneous, natural seasonal thymectomy? Acta Anat. (Basel). 83:1972;593-605.
48. Muller-Hermelink H.K., Steinmann G.G., Stein H. Structural and functional alterations of the ageing human thymus. Adv. Exp. Med. Biol. 149:1982;303-312.
49. Steinmann G.G., Muller-Hermelink H.K. Immunohistological demonstration of terminal transferase (TdT) in the age-involuted human thymus. Immunobiology. 126:1984;45-52.
50. Bertho J.M., Demarquay C., Moulian N., Van Der Meeren A., Berrih-Aknin S., Gourmelon P. Phenotypic and immunohistological analyses of the human adult thymus: evidence for an active thymus during adult life. Cell Immunol. 179:1997;30-40.
51. Jamieson B.D., Douek D.C., Killian S., Hultin L.E., Scripture-Adams D.D., Giorgi J.V.et al. Generation of functional thymocytes in the human adult. Immunity. 10:1999;569-575.
52. + T-lymphocyte regeneration after intensive chemotherapy. N. Engl. J. Med. 332:1995;143-149.
53. Shortman K., Egerton M., Spangrude G.J., Scollay R. The generation and fate of thymocytes. Semin. Immunol. 2:1990;3-12.
54. Scollay R.G., Butcher E.C., Weissman I.L. Thymus cell migration. Quantitative aspects of cellular traffic from the thymus to the periphery in mice. Eur. J. Immunol. 10:1980;210-218.
55. Tough D.F., Sprent J. Life span of naive and memory T cells. Stem Cells. 13:1995;242-249.
56. Miller R.A. The aging immune system: primer and prospectus. Science. 273:1996;70-74.
57. Pawelec G., Effros R.B., Caruso C., Remarque E., Barnett Y., Solana R. T cells and aging (update February 1999). Front Biosci. 4:1999;D216-69.
58. + T cells correlates with shifts in the frequencies of cell subsets defined by membrane CD44, CD45RB, 3G11, and MEL-14 expression. J. Immunol. 151:1993;575-587.
59. Kubo M., Cinader B. Polymorphism of age-related changes in interleukin (IL) production: differential changes of T helper subpopulations, synthesizing IL 2, IL 3 and IL 4a. Eur. J. Immunol. 20:1990;1289-1296.
60. Chang M.P., Utsuyama M., Hirokawa K., Makinodan T. Decline in the production of interleukin-3 with age in mice. Cell Immunol. 115:1988;1-12.
61. Shi J., Miller R.A. Differential tyrosine-specific protein phosphorylation in mouse T lymphocyte subsets: effect of age. J. Immunol. 151:1993;730-739.
62. Utsuyama M., Varga Z., Fukami K., Homma Y., Takenawa T., Hirokawa K. Influence of age on the signal transduction of T cells in mice. Int. Immunol. 5:1993;1177-1182.
63. Patel H.R., Miller R.A. Age-associated changes in mitogen-induced protein phosphorylation in murine T lymphocytes. Eur. J. Immunol. 22:1992;253-260.
64. Engwerda C.R., Handwerger B.S., Fox B.S. Aged T cells are hyporesponsive to costimulation mediated by CD28. J. Immunol. 152:1994;3740-3747.
65. hi T lymphocytes accumulate with age in mice and respond poorly to concanavalin A. Eur. J. Immunol. 19:1989;977-982.
66. Thoman M.L., Weigle W.O. Cell-mediated immunity in aged mice: an underlying lesion in IL-2 synthesis. J. Immunol. 128:1982;2358-2361.
67. + T cells from young and aged mice. J. Immunol. 145:1990;1295-1302.
68. Li S.P., Cai Z., Shi W., Brunmark A., Jackson M., Linton P.-J. Early antigen-specific response by naive CD8 T cells is not altered with aging. J. Immunol. 168:2002;6120-6127.
69. Haynes B.F., Markert M.L., Sempowski G.D., Patel D.D., Hale L.P. The role of the thymus in immune reconstitution in aging, bone marrow transplantation, and HIV-1 infection. Annu. Rev. Immunol. 18:2000;529-560.
70. Jotereau F.V., Heuze F., Salmon-vie V., Gascan H. Cell kinetics in the fetal mouse thymus: precursor cell input, proliferation, and emigration. J. Immunol. 138:1987;1026-1030.
71. Donskoy E., Goldschneider I. Thymocytopoiesis is maintained by blood-borne precursors throughout postnatal life. A study in parabiotic mice. J. Immunol. 148:1992;1604-1612.
72. Blomberg M., Rao S., Reilly J., Tiarks C., Peters S., Kittler E.et al. Repetitive bone marrow transplantation in nonmyeloablated recipients. Exp. Hematol. 26:1998;320-324.
73. Foss D.L., Donskoy E., Goldschneider I. The importation of hematogenous precursors by the thymus is a gated phenomenon in normal adult mice. J. Exp. Med. 193:2001;365-374.
74. Goldschneider I., Komschlies K.L., Greiner D.L. Studies of thymocytopoiesis in rats and mice. I. Kinetics of appearance of thymocytes using a direct intrathymic adoptive transfer assay for thymocyte precursors. J. Exp. Med. 163:1986;1-17.
75. Jotereau F.V., LeDouarin N.M. Demonstration of a cyclic renewal of the lymphocyte precursor cells in the quail thymus during embryonic and perinatal life. J. Immunol. 129:1982;1869-1877.
76. Bechtold T.E., Smith P.B., Turpen J.B. Differential stem cell contributions to thymocyte succession during development of Xenopus laevis. J. Immunol. 148:1992;2975-2982.
77. Tanchot C., Rocha B. Peripheral selection of T cell repertoires: the role of continuous thymus output. J. Exp. Med. 186:1997;1099-1106.
78. McFarland R.D., Picker L.J., Koup R.A., Douek D.C. Recently identified measures of human thymic function. Clin. Appl. Immunol. 2:2001;65-73.
79. Douek D.C., McFarland R.D., Keiser P.H., Gage F.A., Massey J.M., Haynes B.F.et al. Changes in thymic function with age and during the treatment of HIV infection. Nature. 396:1998;690-695.
80. Erkeller-Yuksel F.M., Deneys V., Yuksel B., Hannet I., Hulstaert F., Hamilton C.et al. Age-related changes in human blood lymphocyte subpopulations. J. Pediatr. 120:1992;216-222.
81. Rocha B., Dautigny N., Pereira P. Peripheral T lymphocytes: expansion potential and homeostatic regulation of pool sizes and CD4/CD8 ratios in vivo. Eur. J. Immunol. 19:1989;905-911.
82. Freitas A.A., Rocha B. Lymphocyte lifespans: homeostasis selection and competition. Immunol. Today. 14:1993;25-29.
83. Smith H., Chen I.-M., Kubo R., Tung K.S. Neonatal thymectomy results in a repertoire enriched in T cells deleted in adult thymus. Science. 245:1989;749-752.
84. + T cell maturation. Mech. Ageing Develop. 96:1997;75-88.
85. Franceschi C., Monti D., Barbieri D., Salvioli S., Grassilli E., Capri M.et al. Successful immunosenescence and the remodelling of immune response with ageing. Nephrol. Dial. Transplant. 11(Suppl. 9):1996;18-25.
86. Gabor M.J., Scollay R., Godfrey D.I. Thymic T cell export is not influenced by the peripheral T cell pool. Eur. J. Immunol. 27:1997;2986-2993.
87. Mehr R., Perelson A.S., Fridkishareli M., Globerson A. Feedback regulation of T cell development: manifestations in aging. Mech. Ageing Develop. 91:1996;195-210.
88. Utsuyama M., Kobayashi S., Hirokawa K. Induction of thymic hyperplasia and suppression of splenic T cells by lesioning of the anterior hypothalamus in aging Wistar rats. J. Neuroimmunol. 77:1997;174-180.
89. Madden K.S., Bellinger D.L., Felten S.Y., Snyder E., Maida M.E., Felten D.L. Alterations in sympathetic innervation of thymus and spleen in aged mice. Mech. Ageing Develop. 94:1997;165-175.
90. Flexner C. HIV protease inhibitors. N. Engl. J. Med. 338:1998;1281-1292.
91. Al-Harthi L., Marchetti G., Steffens C.M., Poulin J., Sekalv R., Landav A. Detection of T cell receptor circles (TRECs) as biomarkers for de novo T cell synthesis using a quantitative polymerase chain reaction-enzyme linked immunosorbent assay (PCR-ELISA). J. Immunol. Meth. 237:2000;187-197.
92. Franco J.M., Rubio A., Martinez-Moya M., Leal M., Merchante E., Sanchez-Quijano A.et al. T-cell repopulation and thymic volume in HIV-1-infected adult patients after highly active antiretroviral therapy. Blood. 99:2002;3702-3706.
93. Zhang L., Lewin S.R., Markowitz M., Lin H.H., Skulsky E., Karanicolas R.et al. Measuring recent thymic emigrants in blood of normal and HIV-1-infected individuals before and after effective therapy. J. Exp. Med. 190:1999;725-732.
94. Poulin J.F., Viswanathan M.N., Harris J.M., Komanduri K.V., Wieder E., Ringuette N.et al. Direct evidence for thymic function in adult humans. J. Exp. Med. 190:1999;479-486.
95. Choyke P.L., Zeman R.K., Gootenberg J.E., Greenberg J.N., Hoffer F., Frank J.A. Thymic atrophy and regrowth in response to chemotherapy: CT evaluation. AJR Am. J. Roentgenol. 149:1987;269-272.
96. Kissin C.M., Husband J.E., Nicholas D., Eversman W. Benign thymic enlargement in adults after chemotherapy: CT demonstration. Radiology. 163:1987;67-70.
97. Small E.J., Venook A.P., Damon L.E. Gallium-avid thymic hyperplasia in an adult after chemotherapy for Hodgkin disease. Cancer. 72:1993;905-908.
98. Simmonds P., Silberstein M., McKendrick J. Thymic hyperplasia in adults following chemotherapy for malignancy. Aust. NZ J. Med. 23:1993;264-267.
99. Tait D.M., Goldstraw P., Husband J.E. Thymic rebound in an adult following chemotherapy for testicular cancer. Eur. J. Surg. Oncol. 12:1986;385-387.
100. Douek D.C., Vesico R.A., Betts M.R., Brenchley J.M., Hill B.J., Zhang L.et al. Assessment of thymic output in adults after haematopoietic stem cell transplantation and prediction of T-cell reconstitution. Lancet. 355:2000;1875-1881.
101. Weinberg K., Blazar B.R., Wagner J.E., Agura E., Hill B.J., Smogorzewska M.et al. Factors affecting thymic function after allogeneic hematopoietic stem cell transplantation. Blood. 97:2001;1458-1466.
102. McCune J.M., Loftus R., Schmidt D.K., Carroll P., Webster D., Swor-Yim L.B.et al. High prevalence of thymic tissue in adults with HIV-1 infection. J. Clin. Invest. 101:1998;2301-2308.
103. Douek D.C., Koup R.A. Evidence for thymic function in the elderly. Vaccine. 18:2000;1638-1641.
104. + T cell homeostasis and function in advanced HIV disease. Science. 277:1997;112-116.
105. Hakim F.T., Cepeda R., Kaimei S., Mackall C.L., McAtee N., Zujewski J.et al. Constraints on CD4 recovery postchemotherapy in adults: thymic insufficiency and apoptotic decline of expanded peripheral CD4 cells. Blood. 90:1997;3789-3798.
106. Stoddart C.A., Liegler T.J., Mammano F., Linquist-Stepps V.D., Hayden M.S., Deeks S.G.et al. Impaired replication of protease inhibitor-resistant HIV-1 in human thymus. Nat. Med. 7:2001;712-718.
107. Hirokawa K., Utsuyama M., Kasai M., Kurashima C., Ishijima S., Zeng Y.X. Understanding the mechanism of the age-change of thymic function to promote T cell differentiation. Immunol. Lett. 40:1994;269-277.
108. Goverman J., Brabb T., Huseby E.S., Farr A.G. TCR signaling regulates thymic organization: lessons from TCR-transgenic mice. Immunol. Today. 18:1997;204-208.
109. Aspinall R. Age-associated thymic atrophy in the mouse due to a deficiency affecting rearrangement of the TCR during intrathymic T cell development. J. Immunol. 158:1997;3037-3045.
110. George A.J.T., Ritter M.A. Thymic involution with ageing: obsolescence or good housekeeping? Immunol. Today. 17:1996;267-272.
111. Turke P.W. Thymic involution. Immunol. Today. 18:1997;407.
112. Brearley S., Gentle T.A., Baynham M.I., Roberts K.D., Abrams L.D., Thompson R.A. Immunodeficiency following neonatal thymectomy in man. Clin. Exp. Immunol. 70:1987;322-327.
113. Herrmann D.N., Carney P.R., Wald J.J. Juvenile myasthenia gravis: treatment with immune globulin and thymectomy. Pediatr. Neurol. 18:1998;63-66.
114. Jaretzki A. III, Aarli J.A., Kaminski H.J., Phillips L.H. II, Sanders D.B. Thymectomy for myasthenia gravis: evaluation requires controlled prospective studies. Ann. Thorac. Surg. 76:2003;1-3.
115. Hong R. The thymus. Finally getting some respect. Chest Surg. Clin. N. Am. 11:2001;295-310.
116. Markert M.L., Boeck A., Hale L.P., Kloster A.L., McLaughlin T.M., Batchvarova M.N.et al. Transplantation of thymus tissue in complete DiGeorge syndrome. N. Engl. J. Med. 341:1999;1180-1189.