Suppressor T cell growth and differentiation. Identification of a cofactor required for suppressor T cell function and distinct from interleukin 2.
This report describes a Ts costimulator assay and its use to analyze cofactors required for the expression of suppressor T cell function. Activation of primed MLR-Ts (alloantigen-activated suppressor T cells suppressive of mixed leukocyte reaction) to suppressor T cell factor (TsF) production typically fails in the presence of glutaraldehyde-fixed rather than irradiated allogeneic stimulator cells. However, MLR-TsF production was restored by the addition of 48-h primary MLR supernates; MLR-derived Ts costimulator neither activated primed MLR-Ts in the absence of fixed allogeneic stimulators nor directly suppressed assay MLR. Lack of antigen specificity or genetic restriction and failure to activate unprimed MLR-Ts precursors suggested that Ts costimulator activity differed from previously described Ts inducer functions and was more closely aligned with the lymphocyte- or monocyte-derived interleukins (IL). Three findings distinguished Ts costimulator from IL-2. Depletion of IL-2 activity from MLR supernates by HT2 adsorption failed to affect Ts costimulator function. In addition, MLR supernates prepared in the presence of cyclosporin A contained no IL-2 but expressed Ts costimulator activity. Finally, gel chromatography demonstrated Ts costimulator in peaks of 21,000 and 43,000 mol wt that were largely distinct from the IL-2-containing fractions. Ts costimulator activity was also identified in phorbol myristate acetate (PMA)-induced EL4 supernates and was retained in those supernates after IL-2 depletion by HT2 adsorption. In preliminary functional characterization, MLR supernate-derived Ts costimulator triggered MLR-TsF production from irradiated MLR-Ts in the absence of proliferation. Thus a differentiative rather than proliferative stimulus required for primed MLR-Ts function appears to be provided by this Ts costimulator and has been provisionally termed Ts differentiative factor ( TsDF ). This initial characterization may thus identify one of a possibly distinctive family of interleukins required in the alloantigen-driven activation of suppressor T cells to effector function.
D000818:Animals; D000950:Antigens, Ly / Q000276:immunology; D002454:Cell Differentiation; D002460:Cell Line; D000939:Epitopes; D007376:Interleukin-2 / Q000502:physiology*; D007519:Isoantigens / Q000276:immunology; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D008222:Lymphokines / Q000096:biosynthesis / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013491:Suppressor Factors, Immunologic; D050378:T-Lymphocytes, Regulatory / Q000145:classification / Q000166:cytology / Q000276:immunology*; D013945:Thymoma / Q000276:immunology
D000950:Antigens, Ly; D000939:Epitopes; D007376:Interleukin-2; D007519:Isoantigens; D008222:Lymphokines; D013491:Suppressor Factors, Immunologic