T cells affect thymic involution during puberty by inducing regression of the adrenal reticularis
The thymus involutes after puberty, although the mechanism by which this process occurs remains poorly understood. The profile of thymic involution, which is inversely correlated with an increase in peripheral T cells, may indicate that the accumulation of T cells in the periphery is related to thymic atrophy. In this study, it was shown that the prevention of T cell generation delayed the initiation of thymic involution. The activation of T cells increased the serum concentration of glucocorticoid (GC) and thymic involution, which was completely prevented by adrenalectomy. In the adrenals of growing mice, the activity of the zona fasciculata, which produces GC, increased and plateaued by the weaning period; however, the zona reticularis (ZR), which produces dehydroepiandrosterone (DHEA) that has anti-GC actions, started to decline just before puberty. Thymic atrophy was preceded by the infiltration of activated T cells into the ZR and by the loss of ZR cells. Thus, T cells are involved in thymic involution, a process which was retarded by DHEA administration, through an increase in GC activity due to ZR cell-killing.
KeywordsThymic involution T cell-mediated stress GC/DHEA ratio Dynamics of adrenal cortex
The authors would like to thank Dr. Katsuiku Hirokawa (Emeritus Professor of Tokyo Medical and Dental University), Institute for Health and Life Sciences, Tokyo, Japan, for useful discussions and a critical reading of the manuscript. Thanks are also due to Dr. Shigeyasu Tanaka, Faculty of Science, Shizuoka University, Shizuoka, Japan, for helpful comments and technical advice.
- 2.Macieira-Coelho A (2003) The immune theory. In: Macieira-Coelho A (ed) Biology of aging. Progress in Molecular and Subcellular Biology: Cell Immortalization, vol 30. Springer, HeidelbergGoogle Scholar
- 3.Henson SM, Aspinall R (2003) Aging and the immune system. In: Aspinall R (ed) Aging of organs and system. Kluwer, DordrechtGoogle Scholar
- 4.Mitchell WA, Aspinall R (2007) Immunosenescence, thymic involution and autoimmunity. In: Pawelec G (ed) Immunosenescence. Springer, New YorkGoogle Scholar
- 13.Andres R, Tobin JD (1977) Endocrine system. In: Finch CE, Hayflick L (eds) Handbook of the biological aging. Van Nostrand Reinhold, New YorkGoogle Scholar
- 30.Laccorazza HD, Patiño JAG, Weksler ME, Radu D, Nikolić-Žugić J (1999) Failure of rearranged TCR transgenes to prevent age-associated thymic involution. J Immunol 163:4262–4268Google Scholar
- 32.Endoh A, Kristiansen SB, Casson PR, Buster JE, Hornsby PJ (1996) The zona reticularis is the site of biosynthesis of dehydroepiandrosterone and dehydroepiandrosterone sulfate in the adult human adrenal cortex resulting from its low expression of 3 beta-hydroxysteroid dehydrogenase. J Clin Endocrinol Metab 81:3558–3565PubMedCrossRefGoogle Scholar
- 35.Rouse RV (1985) Is Ia antigen expression by thymic epithelial cells constitutive? In: Klaus GGB (ed) Microenvironment in the lymphoid system. Advances in. Experimental Medicine and Biology, vol 186. Plenum, New YorkGoogle Scholar
- 37.Wolkersdörfer GW, Lohmann T, Marx C, Schröder S, Pfeiffer R, Stahl HD, Scherbaum WA, Chrousos GP, Bornstein SR (1999) Lymphocytes stimulate dehydroepiandrosterone production through direct cellular contact with adrenal zona reticularis cells: a novel mechanism of immune-endocrine interaction. J Clin Endocrinol Metab 84:4220–4227PubMedCrossRefGoogle Scholar