Humoral mechanisms in T cell vaccination: induction and functional characterization of anti-lymphocytic autoantibodies.
T cell vaccination, the application of syngeneic attenuated T cells, has 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 vaccination in the Lewis rat induced autoantibodies reactive with several syngeneic T cell proteins. These autoantibodies were not detectable in normal Lewis sera as assessed by immunoblotting and flow cytometry with intact 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 preformed humoral network by T cell vaccination. Recovery from passively or actively induced experimental autoimmune encephalomyelitis (EAE) in the Lewis rat, too, could be shown to be associated with the development of 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 kinds of sera were able to ameliorate EAE. This protective effect of the post-vaccination sera was not idiotype-specific, since sera obtained after T cell vaccination with an unrelated T cell clone were similarly effective in suppressing EAE. These results suggest that anti-lymphocytic antibodies might play an immunoregulatory role that can be positively manipulated by T cell vaccination.
Herkel
J
J
Department of Medicine, Johannes Gutenberg University, Mainz, Germany.
Brunner
S
S
Meyer zum Büschenfelde
K H
KH
Lohse
A W
AW
D000818:Animals; D000961:Antilymphocyte Serum / Q000096:biosynthesis* / Q000737:chemistry* / Q000502:physiology; D001323:Autoantibodies / Q000096:biosynthesis* / Q000737:chemistry* / Q000502:physiology; D002999:Clone Cells / Q000637:transplantation; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000097:blood / Q000276:immunology / Q000628:therapy; D007106:Immune Sera / Q000494:pharmacology; D007130:Immunoglobulin Idiotypes / Q000096:biosynthesis / Q000737:chemistry; D008213:Lymphocyte Activation; D008565:Membrane Proteins / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000637:transplantation*; D014611:Vaccination
D000961:Antilymphocyte Serum; D001323:Autoantibodies; D007106:Immune Sera; D007130:Immunoglobulin Idiotypes; D008565:Membrane Proteins