@misc{oai:niigata-u.repo.nii.ac.jp:00005306,
 author = {Kushida, Yoshihiro},
 month = {Mar},
 note = {T cell dependent immune functions gradually decline with age. The thymus that produces T cells involutes after puberty, resulting in declines of thymic functions with age. It is thought that changes in the production of immunoregulatory hormones, including glucocorticoid (GC) that induces thymocyte death, result in thymic involution with age. However, it is possible that these hormones are not enough for this process because the amount of GC in the sera at a normal physiological state rarely increases with age. Recently, mice with abnormalities in the generation of a normal T cell repertoire are reported to not show thymic involution after puberty. Furthermore, the profile of thymic involution is inversely correlated with an increase in peripheral T cells. These results may indicate that a lack of functional, mature T cells in the periphery does not cause age-related thymic involution, suggesting that, during ontogeny, the gradual generation of peripheral T cells that encounter various environmental antigens can be activated and cause the post-puberty involution of the thymus. Based on this idea, I studied involvement of peripheral T cells in thymic involution after puberty. I found that the prevention of T cell generation delayed the initiation of thymic involution. On the other hand, the activation of T cells by anti-CD3 antibodies increased the serum concentration of GC and thymic atrophy, 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. These changes reflect the amounts of blood-circulating hormones. Thymic involution was significantly retarded by DHEA administration. The involution of ZR with age was not observed in athymic nude mice. However, the repopulation of T cells resulted in its atrophy. Thymic atrophy after immune stimulation was preceded continuously by the infiltration of activated T cells into the ZR, by the expression of the major histocompatibility complex (MHC) class II on ZR cells, and by the loss of ZR cells by apoptosis. Thus, T cells are involved in thymic involution through an increase in GC activity due to ZR cell-killing., 新潟大学大学院自然科学研究科, 平成24年3月23日, 新大院博（理）甲第349号, 新大院博（理）甲第349号},
 title = {Thymic involution with age : regression of the adrenal reticularis by peripheral T cells},
 year = {2012}
}