Antigen-specific inhibition of immune interferon production by suppressor cells of autoimmune encephalomyelitis.
Previous work from this laboratory has revealed that spleen and/or lymph node cells from Lewis rats, that have recovered from an acute episode of experimental autoimmune encephalomyelitis (EAE), suppress the development of EAE when injected into syngeneic recipients subsequently challenged with myelin basic protein (MBP) in CFA. In an effort to understand the mechanism of this suppression, we measured the production of immune IFN-gamma, which may be required for the induction of an immune response, by EAE effector T cells (which transfer disease) and EAE suppressor cells when cultured in vitro with MBP. We now report that EAE effector T cells produce IFN-gamma when cultured in vitro with MBP. In contrast, spleen cells from recovered rats (which manifest suppressor activity in vivo) do not produce IFN-gamma. Moreover, in cell mixing experiments, these suppressor spleen cells inhibited the production of IFN-gamma by EAE effector cells. This inhibition was not eliminated by the removal of macrophages nor by the inhibition of PG synthesis by indomethacin. Furthermore, the inhibition was shown to be Ag-specific and mediated by nylon-adherent, radiation-sensitive splenic T cells. The findings suggest that suppressor cells regulate EAE by inhibiting IFN-gamma production by effector cells. This inhibition may result in the down-regulation of IFN-gamma-induced expression of class II major histocompatibility Ag on cells of the central nervous system, thus reducing the presentation of tissue-specific Ag (i.e., MBP) to autoreactive lymphocytes.
D000208:Acute Disease; D000818:Animals; D000941:Antigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005260:Female; D007116:Immunization, Passive; D007371:Interferon-gamma / Q000096:biosynthesis*; D010047:Ovalbumin / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000637:transplantation
D000941:Antigens; D007371:Interferon-gamma; D010047:Ovalbumin