TYPE-2 IMMUNE DEVIATION HAS DIFFERENTIAL-EFFECTS ON ALLOREACTIVE CD4(-CELLS() AND CD8(+) T)

Allograft rejection has been associated with detection of the type 1 l ymphokines, IFN-gamma and IL-2, The role of type 2 cytokines (IL-4 and IL-5) remains controversial, as is whether alloreactive CD4(+) and CD 8(+) T cells behave similarly when exposed to type 2 cytokine-enhancin g manipulations. We studied the characteristics of alloreactive CD4(+) and CD8(+) T cells before and after type 2 immune deviation induced b y IL-4 plus anti-IFN-gamma Ab, Alloreactive T cells from naive mice we re low in frequency, produced only IL-2, and were predominantly CD4(+) , while alloreactive T cells from allograft-primed mice were high in f requency, produced IFN-gamma, IL-2, and IL-4, and were predominantly C D8(+), Type 2 immune deviation of allospecific CD4(+) T cells resulted in IL-4 and IL-5 production without IFN-gamma, consistent with unipol ar type 2 immunity. These T cells mediated delayed-type hypersensitivi ty, but not cytotoxicity, Under identical type 2 cytokine-inducing con ditions, allospecific CD8(+) T cells were primed to become IL-4, IL-5, and IFN-gamma producers, and exhibited cytotoxicity, but not classic delayed-type hypersensitivity. Adoptive transfer of either cell popula tion into SCID recipients of allogeneic skin resulted in graft rejecti on, with stable allospecific type 2 cytokine production in vivo. Adopt ive transfer of the IL-4/IL-5-producing CD4(+) T cells, but not the CD 8(+) T cells, induced a distinct histopathology characterized by marke d eosinophilic infiltration of the skin. We conclude that type 2 immun e deviation has differential effects on CD4(+) and CD8(+) T cells and results in emergence of alternate effector mechanisms capable of destr oying allografts.