TY - JOUR
T1 - Staphylococcal enterotoxin B and tumor‐necrosis factor‐α‐induced relapses of experimental allergic encephalomyelitis
T2 - Protection by transforming growth factor‐β and interleukin‐10
AU - Crisi, Giovanna M.
AU - Santambrogio, Laura
AU - Hochwald, Gerald M.
AU - Smith, Sidney R.
AU - Carlino, Joseph A.
AU - Thorbecke, G. Jeanette
PY - 1995/11
Y1 - 1995/11
N2 - 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.
AB - 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.
KW - Autoimmunity
KW - Experimental allergic encephalomyelitis
KW - Interleukin‐10
KW - Transforming growth factor‐β
KW - Tumor necrosis factor‐α
UR - http://www.scopus.com/inward/record.url?scp=0028783962&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0028783962&partnerID=8YFLogxK
U2 - 10.1002/eji.1830251108
DO - 10.1002/eji.1830251108
M3 - Article
C2 - 7489740
AN - SCOPUS:0028783962
SN - 0014-2980
VL - 25
SP - 3035
EP - 3040
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 11
ER -