TGF-beta promotes immune deviation by altering accessory signals of antigen-presenting cells.

Macrophages incubated with OVA in the presence of TGF-beta2 induce immune deviation in vivo (impaired delayed hypersensitivity and IgG2a Ab production) when injected into naive, syngeneic mice. OVA-specific TCR transgenic naive T cells (DO11.10 T cells) produce Th1-type cytokines when stimulated in vitro with OVA-pulsed peritoneal exudate cells (PEC), but if PEC are first treated with TGF-beta2 and then pulsed with OVA, the T cells secrete Th2-type cytokines instead. In this study, we investigated the mechanisms that are involved in the modified Ag-presenting functions of macrophages by TGF-beta2 pretreatment. We have found that: 1) TGF-beta2 impaired the capacity of PEC to produce IL-12 and to express CD40; 2) reduced CD40 expression on TGF-beta2-treated PEC impaired IL-12 production when the cells were cocultured with DO11.10 T cells; 3) the failure of TGF-beta2-treated PEC to stimulate DO11.10 T cells to secrete IFN-gamma was due to their impaired IL-12 production. From these results, we conclude that TGF-beta2 treatment impairs the ability of macrophages to produce IL-12 and to express CD40. As a consequence, TGF-beta2-treated PEC fail to promote development of pT cells toward the Th1 phenotype.

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