Staphylococcal enterotoxin B and tumor‐necrosis factor‐α‐induced relapses of experimental allergic encephalomyelitis: Protection by transforming growth factor‐β and interleukin‐10

Giovanna M. Crisi, Laura Santambrogio, Gerald M. Hochwald, Sidney R. Smith, Joseph A. Carlino, G. Jeanette Thorbecke

Research output: Contribution to journalArticle

95 Scopus citations

Abstract

A study was made of the ability of the superantigen staphylococcal enterotoxin B (SEB) to induce relapses of experimental allergic encephalomyelitis (EAE) in SJL mice that had partially or completely recovered from acute EAE. We find that a single injection of 0.05 mg SEB i.v. induces mild relapses in 50% of such mice. In addition, tumor necrosis factor (TNF)‐α (0.2 μg, i.p.) also induces EAE relapses in 43% of SJL mice when injected 1–2 months after recovery. SEB does not induce a second relapse if reinjected when Vβ17a+ T cells are still partially deleted. In these mice, however, TNF‐α is equally effective in inducing relapses as in mice that did not receive SEB previously. We showed earlier that transforming growth factor (TGF)‐β and TNF‐α have antagonistic effects on experimental autoimmune diseases; e.g., in spontaneously relapsing EAE, TGF‐β and anti‐TNF were protective, while anti‐TGF‐β caused disease exacerbation. Interleukin (IL)‐10 is also known to counteract certain TNF effects. We now find that both human IL‐10 and TGF‐β2 lower the incidence of EAE relapses when given simultaneously with SEB or TNF‐α. The protective effect of TGF‐β is significant only against relapses induced by SEB (reduced to 9%), and that of IL‐10 only against relapses induced by TNF (reduced to 0%) with the treatment regimens employed. Neutralizing anti‐TGF‐β does not increase the incidence of SEB‐induced EAE relapses. In contrast, anti‐IL‐10 increases both the incidence and the severity of such relapses. We conclude that TNF production is probably important in causing EAE relapses, but that other aspects of the SEB‐induced reactivation of myelin‐specific T cells also contribute. Furthermore, endogenous IL‐10 rather than TGF‐β production appears to limit the susceptibility to induction of EAE relapses in this model.

Original languageEnglish (US)
Pages (from-to)3035-3040
Number of pages6
JournalEuropean Journal of Immunology
Volume25
Issue number11
DOIs
StatePublished - Nov 1995

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Keywords

  • Autoimmunity
  • Experimental allergic encephalomyelitis
  • Interleukin‐10
  • Transforming growth factor‐β
  • Tumor necrosis factor‐α

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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