Involvement of thyroid hormones in the expression of MHC class I antigens during ontogeny in Xenopus.

Louise A Rollins-Smith,Patrick J Blair,Martin F Flajnik,A Tray Davis,Wayne F Green

doi:10.1155/1997/38464

Abstract

The major histocompatibility complex (MHC) is a cluster of genes encoding products central to all major functions of the vertebrate immune system. Evidence for an MHC can be found in all vertebrate groups that have been examined except the jawless fishes. Expression of MHC class I and class II antigens early in ontogeny is critically important for development of T lymphocytes capable of discriminating self from nonself. Because of this essential role in T-cell development, the ontogeny of MHC expression in the South African clawed frog, Xenopus laevis, was studied. Previous studies of MHC class I expression in Xenopus laevis suggested that class I antigens are virtually absent from tadpole tissues until climax of metamorphosis. We therefore examined the possible role of thyroid hormones (TH) in the induction of class I. By flow cytometry, a small amount of class I expression was detectable on splenocytes and erythrocytes in untreated frogs at prometamorphic stages 55-58, and the amount increased significantly at the conclusion of metamorphic climax. Thus, metamorphosis is associated with increased intensity of class I expression. Neither inhibition nor acceleration of metamorphosis altered the timing of onset of class I expression. However, inhibition of metamorphosis prevented the increase in class I expression characteristic of adult cell populations. Because expression was not accelerated in TH-treated frogs or delayed in metamorphosis-inhibited frogs, it is unlikely that TH are the direct developmental cues that induce expression, although they seem to be required for the upregulation of class I expression occurring at metamorphosis. Differences in the pattern of expression in different subpopulations of cells suggest a complex pattern of regulation of expression of class I antigens during ontogeny.

Highlights

Because amphibians evolved to exploit temporary ponds as a developmental niche for their larval stages, a functional immune system that develops quickly is necessary to enable them to respond to potential pathogens in that environment
The increased expression on postmetamorphic thymocytes reflects an increase in the number of positive cells rather than increased expression on individual cells. These studies examined the possible role of thyroid hormones in the regulation of expression of major histocompatibility complex (MHC) class antigens
Because the splenocytes and erythrocytes recovered from older perchlorate-blocked frogs (148-224 days of age) did not show the increased expression of class antigens characteristic of postmetamorphic adults, thyroid hormones may be involved in regulation of the level of class expression

Summary

Introduction

Because amphibians evolved to exploit temporary ponds as a developmental niche for their larval stages, a functional immune system that develops quickly is necessary to enable them to respond to potential pathogens in that environment. Studies of the ontogeny of the immune system of Xenopus laevis (reviewed in Flajnik et al, 1987; Du Pasquier et al, 1989; Horton, 1994; Rollins-Smith and Cohen, 1995) have demonstrated that the early immune system is not the fully developed mature immune system that will serve adult frogs. Studies in murine systems (reviewed in Schwartz, 1984) have demonstrated that the major histocompatibility complex (MHC) is intimately involved in the selection of T lymphocytes for recognition of self and recognition of foreign antigens in the context of self. In Xenopus, studies involving the fusion of the anterior of one embryo to the posterior of another embryo have revealed that all T-cell precursors pass through the thymus, and resulting mature T cells are "educated" to recognize self and foreign antigens in the context of the MHC expressed by the thymus (Flajnik et al, 1985). Because of the importance of the MHC in the devel’opment of immunological tolerance, it is important to understand when in ontogeny MHC antigens are expressed and what regulates their expression

Methods

Results

Conclusion