Superantigens induce primary T cell responses to soluble autoantigens by a non-V beta-specific mechanism of bystander activation.
Superantigens have been suggested to act as powerful TCR V beta-specific inducers of T cell reactivity in autoimmune diseases. We have investigated the capacity of staphylococcal enterotoxins (SE) to prime autoreactive T cell responses in naive animals in the Lewis rat model of experimental autoimmune encephalomyelitis (EAE), where myelin basic protein (MBP)-specific CD4+ effector T cells express almost exclusively V beta 8.2 TCR elements. By taking advantage of the reactivity of V beta 8.2+ MBP-specific T cells to SEE but not to other SEs in vitro, we estimated the potential of different SEs (SEA, SEB, and SEE) to induce a primary T cell response to soluble MBP in vivo. Upon immunization of naive rats with soluble MBP alone or MBP and SEB (which is only a very weak superantigen for rat T cells), no MBP-responses could be retrieved. Similarly, when coimmunizing naive rats with MBP and V beta 8.2-activating SEE, no autoreactivity was inducible. By contrast, coimmunization of animals with soluble MBP and the superantigen SEA that is strongly activating various T cell subpopulations in Lewis rats but not V beta 8.2+ (i.e., potentially MBP reactive) T cells led to a significant primary MBP-specific T cell autoreactivity. These SEA-induced MBP-reactive T cells expressed V beta 8.2 TCRs at levels similar to those seen in autoreactive T cells conventionally induced by immunization with MBP administered in complete Freund's adjuvant (CFA) and could induce disease in a transfer model of EAE. Thus, our results are consistent with the notion that superantigens are able to induce primary T cell responses to soluble autoantigens by a non-V beta specific mechanism of bystander priming.
Rott
O
O
INSERM U.283, Hôpital Cochin, Université René Descartes, Paris, France.
Mignon-Godefroy
K
K
Fleischer
B
B
Charreire
J
J
Cash
E
E
D000818:Animals; D001921:Brain / Q000276:immunology / Q000378:metabolism; D004768:Enterotoxins / Q000276:immunology; D007114:Immunization; D008213:Lymphocyte Activation; D004676:Myelin Basic Protein / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta; D013154:Spleen / Q000276:immunology; D018089:Superantigens / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D004768:Enterotoxins; D004676:Myelin Basic Protein; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens; C075784:T cell receptor Vbeta8