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Hormone regulation of murine T cells: potent tissue-specific immunosuppressive effects of thyroxine targeted to gut T cells.
Wang J; Klein JR; Department of Biological Science, University of Tulsa,
February 28, 1997
Int Immunol. 1996 Feb;8(2):231-5. Unique Identifier : AIDSLINE

Recent studies in athymic mice indicate that the neuroendocrine hormones thyrotropin-releasing hormone (TRH) and thyroid-stimulating hormone (TSH) can significantly influence the development of lymphoid cells associated with intestinal intraepithelial lymphocytes (IEL). In the present study we have examined the effects of those hormones, as well as of thyroxine (T4), a thyroid-derived hormone regulated by TSH, on IEL development in euthymic mice. As reported here, whereas IEL in euthymic mice were unaffected by TRH and TSH treatment, T4 administered to adult euthymic mice at 3 or 6 weeks of age caused a dramatic reduction in the numbers of TCR alpha beta, CD8 alpha beta IEL, i.e. the same subsets previously shown to be up-regulated ty TRH and TSH in athymic mice. When given to euthymic mice >8 weeks of age, after TCR alpha beta and CD8 alpha beta subsets had reached normal levels, T4 had minimal effect on IEL, suggesting that the mode of action of T4 is directed to developing but not mature IEL. That possibility was confirmed in experiments in which T4 treatment of bone marrow radiation chimeras during an active phase of T cell regeneration temporarily halted all IEL development at a stage characteristic of immature IEL. Most interesting, the immunosuppressive effects of T4 were selectively targeted to the intestinal immune system since T4 had no effect on developing thymocytes or on mature peripheral T cells, in either normal euthymic mice or during hematopoietic reconstitution of radiation chimeras. These findings have implications for understanding intestinal immunity and disease, including chronic intestinal inflammation, in ways not previously appreciated.

Animal Antigens, CD5/DRUG EFFECTS Bone Marrow/IMMUNOLOGY Cell Differentiation/DRUG EFFECTS/IMMUNOLOGY CD8-Positive T-Lymphocytes/CYTOLOGY/*DRUG EFFECTS Immunosuppressive Agents/*PHARMACOLOGY Intestinal Mucosa/CYTOLOGY/*DRUG EFFECTS/*IMMUNOLOGY Mice Mice, Inbred BALB C Organ Specificity/IMMUNOLOGY Radiation Chimera/IMMUNOLOGY Receptors, Antigen, T-Cell, alpha-beta/DRUG EFFECTS Support, U.S. Gov't, P.H.S. Thymus Gland/IMMUNOLOGY Thyroxine/*IMMUNOLOGY/*PHARMACOLOGY JOURNAL ARTICLE