HUMORAL MECHANISMS IN T-CELL VACCINATION - INDUCTION AND FUNCTIONAL-CHARACTERIZATION OF ANTI-LYMPHOCYTIC AUTOANTIBODIES

T cell vaccination, the application of syngeneic attenuated T cells, h as been shown to prevent effectively and treat experimental autoimmune diseases, but its mechanisms of action are poorly understood. Here we present data on the induction of a humoral anti-T cell response by T cell vaccination, capable of strongly inhibiting T cell proliferation and of ameliorating experimental autoimmune disease. T cell vaccinatio n in the Lewis rat induced autoantibodies reactive with several syngen eic T cell proteins. These autoantibodies were not detectable in norma l Lewis sera as assessed by immunoblotting and flow cytometry with int act syngeneic T cells. The autoantibody reactivity was not restricted to one idiotype, was detected as early as 1 week after vaccination and was dominated by IgG, suggesting the boosting of a naturally preforme d humoral network by T cell vaccination. Recovery from passively or ac tively induced experimental autoimmune encephalomyelitis (EAE) in the Lewis rat, too, could be shown to be associated with the development o f anti-T cell autoantibodies. In vitro, both the post-EAE and the post -vaccination sera had a strong suppressive effect on the proliferation of syngeneic T cell clones. This inhibition was shown to be mediated by antibodies and to be partly complement-dependent. In vivo, both kin ds of sera were able to ameliorate EAE. This protective effect of the post-vaccination sera was not idiotype-specific, since sera obtained a fter T cell vaccination with an unrelated T cell clone were similarly effective in suppressing EAE. These results suggest that anti-lymphocy tic antibodies might play an immunoregulatory role that can be positiv ely manipulated by T cell vaccination. (C) 1997 Academic Press Limited .