A NOVEL ROLE FOR TGF-BETA AND IL-10 IN THE INDUCTION OF IMMUNE PRIVILEGE

Immune privilege within the eye is due in large part to Ag-specific, s ystemic down-regulation of Th1 immune responses, a phenomenon termed a nterior chamber-associated immune deviation (ACAID), Since the cytokin e milieu influences Th cell differentiation, we hypothesized that TGF- beta, an immunosuppressive cytokine secreted by ocular cells, determin es the nature of the immune response to Ags introduced into the anteri or chamber, Accordingly, an in vitro model of the eye was used to dete rmine the cytokine profile of ocular APC, TGF-beta preferentially indu ced APC to secrete a Th2-type cytokine, IL-10, and concomitantly suppr essed the production of the Th1-inducing cytokine, IL-12, APC incubate d with TGF-beta and anti-IL-10 Ab lost their ability to induce ACAID, In the absence of TGF-beta, Ag-pulsed APC preferentially secreted IL-1 2 and elicited Ag-specific Th1 responses (i.e., delayed-type hypersens itivity (DTH)), However, APC pulsed with Ag and exogenous IL-10 behave d in a manner similar to ocular APC and induced Ag-specific suppressio n of DTH, The role of IL-10 in ACAID was confirmed in IL-10 knockout m ice, Anterior chamber injection of OVA into IL-10 knockout mice elicit ed normal DTH responses rather than ACAID, Moreover, Ag-pulsed APC fro m IL-10 knockout mice were unable to induce ACAID following in vitro t reatment with TGF-beta, Thus, TGF-beta predisposes ocular APC to secre te IL-10 during Ag processing, This, in turn, directs the immune respo nse away from a Th1 pathway and toward a Th2-like response in which DT H is suppressed.