T cell vaccination in autoimmune diseases.
The effectiveness and the mechanism of T cell vaccination were studied in two experimental models of autoimmune disease. The attempt to modulate autoimmune disease via idiotypic regulation of autoreactive antigen-specific T cells was first shown in the rat experimental autoimmune encephalomyelitis (EAE) model where inactivated EAE-inducing T cells could both immunize and protect rats from EAE. We previously reported that low dose T cell vaccination against EAE in Lewis rats was immunologically specific, long lasting and extremely efficient in preventing adoptive transfer of the disease. In experimental autoimmune uveitis (EAU) T cell vaccination was also found to be effective. In both cases, antigen or mitogen activation of the T cells prior to inoculation was required. In the EAE model, T cell vaccination appeared to be associated with two sets of T lymphocytes (CD4+ CD8- helper and CD4- CD8+ cytotoxic/suppressor cells) which were cloned and found to be specifically reactive to the vaccine cells. These anti-idiotypic T cell clones were able to antagonistically modulate the in vitro proliferation of encephalitogenic Z1a cells. In vivo, transfer of the lymph node cells (from which the anti-idiotypic clones were derived) from vaccinated animals to naive syngeneic recipients conferred resistance to EAE. In the EAU model, we also found a consistent immunological response raised against different activated T cells (four T cell lines with irrelevant specificities and mitogen-activated lymphoid cells) in addition to the anti-idiotypic cells. This response, apparently directed to T cell activation markers, might combine with the anti-idiotypic response to regulate autoimmunity.
Beraud
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Laboratoire d'Immunologie, Faculté de Médecine La Timone, Marseille, France.
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology; D005260:Female; D016219:Immunotherapy, Adoptive; D008213:Lymphocyte Activation; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000276:immunology*; D014605:Uveitis / Q000276:immunology; D014611:Vaccination
D000888:Antibodies, Anti-Idiotypic