TGF-BETA PROMOTES IMMUNE DEVIATION BY ALTERING ACCESSORY SIGNALS OF ANTIGEN-PRESENTING CELLS

Macrophages incubated with OVA in the presence of TGF-beta(2) induce i mmune deviation in vivo (impaired delayed hypersensitivity and IgG2a A b production) when injected into naive, syngeneic mice. OVA-specific T CR transgenic naive T cells (DO11.10 T cells) produce Th1-type cytokin es when stimulated in vitro with OVA-pulsed peritoneal exudate cells ( PEC), but if PEC are first treated with TGF-beta(2) and then pulsed wi th OVA, the T cells secrete Th2-type cytokines instead. In this study, we investigated the mechanisms that are involved in the modified Ag-p resenting functions of macrophages by TGF-beta(2) pretreatment. We hav e found that: 1) TGF-beta(2) impaired the capacity of PEC to produce I L-12 and to express CD40; 2) reduced CD40 expression on TGF-beta(2)-tr eated PEC impaired IL-12 production when the cells were cocultured wit h DO11.10 T cells; 3) the failure of TGF-beta(2)-treated PEC to stimul ate DO11.10 T cells to secrete IFN-gamma was due to their impaired IL- 12 production. From these results, we conclude that TGF-beta(2) treatm ent impairs the ability of macrophages to produce IL-12 and to express CD40. As a consequence, TGF-beta(2)-treated PEC fail. to promote deve lopment of pT cells toward the Th1 phenotype.