BIOLOGICAL CHARACTERISTICS OF AN IMMUNOREGULATORY ACTIVITY SECRETED BY AN AUTOREACTIVE CD4(-CELL CLONE THAT SUPPRESSES AUTOIMMUNE DIABETES IN NONOBESE DIABETIC MICE() T)

We previously reported the generation and characterization of a panel of CD4(+) autoreactive T cell clones that suppress development of auto immune diabetes in non-obese diabetic (NOD) mice, We showed that the p rotective capacity of the T cell clones correlates with secretion of a n activity that potently inhibits allogeneic mixed lymphocyte reaction (allo-MLR). In this report, we describe the biological characteristic s of the allo-MLR inhibitory activity (MLR-IA, short for mixed lymphoc yte reaction inhibitory activity) secreted by the protective T cell cl one, NOD-5, MLR-IA has little effect on initiation of proliferation in an allo-MLR, but it potently inhibits the maintenance and amplificati on of the proliferative response, MLR-IA is also capable of inhibiting concanavalin A (Con A)-stimulated splenic responder T cell proliferat ion, MLR-IA is reversible in vitro and is not restricted by MHC class I or II proteins, MLR-IA does not affect IL-2 receptor expression of r esponding T cells and has no effect on IL-2-dependent proliferation of CTLL-20 T cells, Partially purified MLR-IA inhibits IL-2 production i n a primary allo-MLR, and decreases IFN-gamma production during second ary allo-MLR and Con A activation, whereas it enhances IL-4 production in both primary and secondary Con A activation, MLR-IA is not neutral ized by combination of antibodies specific for transforming growth fac tor-beta, IL-10, tumor necrosis factor-alpha/beta or IFN-gamma suggest ive of a novel activity, MLR-IA is ammonium sulfate precipitable, sens itive to protease digestion and is destroyed by boiling, indicating th at a protein moiety is part of its active structure, Our work suggests that a potentially novel immunoregulatory activity, capable of inhibi ting T lymphocyte proliferation and IFN-gamma production, and stimulat ing IL-4 production, may regulate development of autoimmune diabetes i n NOD mice.