CD4+ suppressor cells inhibit the function of effector cells of experimental autoimmune encephalomyelitis through a mechanism involving transforming growth factor-beta.
Nylon wool adherent, CD4+ T cells from the spleens of rats that have recovered from experimental autoimmune encephalomyelitis (EAE) inhibit the in vitro production of IFN-gamma, but not IL-2, by effector cells of EAE when cocultured in the presence of myelin basic protein Ag. When anti-transforming growth factor-beta (TGF-beta) antibodies are added to the co-cultures, IFN-gamma production is restored to normal levels. Irrelevant control antibodies have no effect. The same pattern of response was obtained with cells incubated in serum-free medium. In other experiments, purified TGF-beta was added to cultures of effector cells in the presence of antigen. TGF-beta inhibited the production of IFN-gamma by these cells in a dose-dependent manner, but had no apparent inhibitory effect on IL-2 production. Finally, supernatants from cultures containing effector cells and CD4+ suppressor cells plus Ag contained measurable amounts of TGF-beta, whereas supernatants from cultures of effector cells plus Ag contained no measurable amounts of TGF-beta. These results suggest that CD4+ Ts cells of EAE regulate effector cells of EAE through a mechanism that involves the secretion of TGF-beta and that the inhibitory function of this cytokine can be reversed with neutralizing antibodies directed against TGF-beta.
Karpus
W J
WJ
Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, MI 48201.
Swanborg
R H
RH
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D051381:Rats; D011917:Rats, Inbred Lew; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000502:physiology*
D007376:Interleukin-2; D016212:Transforming Growth Factor beta; D007371:Interferon-gamma