Several model systems have been described where T cells reactive to an antigen can themselves provoke suppressive immune responses by a second population of T cells that limit further responses to these antigens. T cells reactive to MHC antigens will induce a profound and specific resistance to GVH disease; T cells reactive to the encephalitogenic fragment of myelin basic protein, which usually cause paralytic EAE, induce resistance to EAE; some studies have indicated that in vivo responses to super antigens, involving dramatic increases and decreases in selected V-beta T cell populations cannot be reinduced; there are also demonstrations that immunization with TCR peptides provokes an immune response that inhibits function of T cells expressing selected TCR molecules. While some of these models have been more thoroughly explored than others, in each case, it appears that TCR molecules, or clonally specific peptides derived from them, induce the activation of regulatory T cells having specificity for these TCR markers. Such anti-receptor immune responses may reflect one mechanism underlying self tolerance in the peripheral T cell pool for limiting responses to self and environmental antigens, and it may be the basis of rational approaches for controlling at least some immune disease states. This proposal outlines a series of studies designed to acquire a better understanding of the immunobiology of these regulatory cells; whether these immune resistance models operate by a common mechanism, what the subset requirements are for inducing and executing anti-receptor immunities, whether the targets of immune regulation are associated with TCR molecules; what the TCR beta chain repertoire of regulatory T cells is like, and whether regulator T cells have a regulatory role in the thymus.
| Wilson, D B; Schroder, K; Mueller, D et al. (1998) Analysis of TCR beta chains in Lewis rats with experimental allergic encephalomyelitis. II. Vbeta8.2+ T cells with limited CDR3 N region additions derive from the adult thymus. Eur J Immunol 28:1216-24 |
| Sun, D; Wilson, D B; Cao, L et al. (1998) The role of regulatory T cells in Lewis rats resistant to EAE. J Neuroimmunol 81:177-83 |
| Gold, D P; Schroder, K; Mueller, D B et al. (1996) Analysis of T cell receptor beta chains in the rat: I. Allelic polymorphism of V beta 8.2 is not a predisposing genetic factor in susceptibility to experimental allergic encephalomyelitis. J Neurosci Res 45:700-5 |
| Wilson, D B; Steinman, L; Gold, D P (1993) The V-region disease hypothesis: new evidence suggests it is probably wrong. Immunol Today 14:376-80;discussion 380-2 |
