Effects of staphylococcal enterotoxin B on T cell receptor V beta utilization and clinical manifestations of experimental allergic encephalomyelitis.
Staphylococcal enterotoxin B (SEB) is a superantigen (SA) that up-regulates and then subsequently down-regulates and deletes T cells expressing V beta 8 T cell receptor (TcR) chains (Marrack and Kappler, 1990; Johnson et al., 1991). We have investigated the effect of SEB on experimental allergic encephalomyelitis (EAE) in PL/J mice, where the predominant encephalitogenic T cells are V beta 8+ (Acha Orbea et al., 1988; Zamvil et al., 1988). SEB did not enhance induction of EAE when administered prior to or after immunization for EAE. PL/J mice pretreated with SEB developed anergy and deletion of V beta 8 bearing cells and concomitant reduction in the incidence of EAE. Following SEB pretreatment, a redistribution in the TcR utilization of MBP-specific lymphocytes occurred. As a result, there was a low frequency of V beta 8 and expansion of other, normally less frequent, myelin basic protein (MBP)-specific clones. These observations indicate that systemic exposure to superantigen can influence organ-specific autoimmune diseases. We observed V beta-specific elimination, rather than activation, of autoimmune clones, a finding of potential therapeutic value. Modification of the TcR repertoire by systemic exposure to this SA indicates plasticity of immune reactivity and demonstrates a mechanism by which an environmental exposure (SEB) can influence a genetically determined, T cell mediated autoimmune disease.
Kalman
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B
Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107-5083.
Lublin
F D
FD
Lattime
E
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Joseph
J
J
Knobler
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RL
D000818:Animals; D015704:CD4 Antigens / Q000032:analysis; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology*; D004768:Enterotoxins / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D004676:Myelin Basic Protein / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology
D015704:CD4 Antigens; D004768:Enterotoxins; D004676:Myelin Basic Protein; D016693:Receptors, Antigen, T-Cell, alpha-beta; C026066:enterotoxin A, Staphylococcal; C031818:enterotoxin B, staphylococcal