DYNAMIC REGULATION OF INTESTINAL IMMUNITY BY HORMONES OF THE HYPOTHALAMUS-PITUITARY-THYROID AXIS

The role of the thymus in the development of murine small intestinal i ntraepithelial lymphocytes (IELs) has been a controversial topic for d ecades. This controversy has been further propagated by observations t hat differences in IEL repertoires vary according to the particular at hymic animal model system used to study IELs. In an attempt to underst and the bases for these differences, we have undertaken a series of ex periments designed to explore the extent to which extraimmunologic eve nts, in particular neuroendocrine factors, play a role in the developm ent of extrathymic IELs. As discussed here, these studies indicate tha t hormones of the hypothalamus-pituitary-thyroid (HPT) axis exert eith er positive or negative regulatory effects on intestinal IELs, dependi ng upon the particular hormone. Although the mechanisms by which HPT h ormones influence IEL development and immune regulation have yet to be fully delineated, it appears that thyroid-stimulating hormone is a ke y mediator in this process, and that this may occur via local autocrin e/paracrine responses within the intestine itself. The implications of these findings in the context of immunity and disease at the level of the gastrointestinal tract are discussed. (C) 1997 Elsevier Science L td.