Hormonal Regulation of Extrathymic Gut T Cell Development: Involvement of Thyroid Stimulating Hormone

We recently demonstrated that athymic mice which lack intraepithelial lymphocytes (IELs) considered to be thymus-dependent (TD) T cells develop those cells following exogenous treatment with the hypothalamic-derived neuropeptide, thyrotropin-releasing hormone (TRH). To explore the mechanism by which neuroendocrine (NE) hormones influence the development of IELs, we have studied the effects of thyroid-stimulating hormone (TSH), a pituitary hormone that is regulated by TRH, on IEL development in adult mice that were neonatally thymectomized (NTX). Adult NTX mice treated with exogenous TSH for 3 weeks developed normal proportions and numbers of TD (TCRαβ+, CD8αβ+, CD5+, and Thy-1+) IELs in a manner similar to that of TRH-treated NTX mice. The effect of hormone therapy was long-lasting in that IEL subsets which developed during TRH treatment were present well after the known lifespan of TSH in vivo, and because the numbers of IEL remained higher than in untreated mice. These findings suggest that TD IELs develop extrathymically through a series of immunologic and hormonal interactions which are regulated by the thymus during some phase of embryonic life.