Alterations in Cytokine Production Following Intraocular Injection of Soluble Protein Antigen: Impairment in IFN-γ and Induction of TGF-β and IL-4 Production

Immune deviation induced by intraocular injection of soluble protein Ag, referred to as anterior chamber-associated immune deviation (ACAID), is characterized by impairment of delayed hypersensitivity (DH). Two populations of splenic regulatory cells that impair the induction and expression phases of DH are involved in the ACAID response and may mediate their effects through cytokines. The purpose of the present study was to evaluate the role that cytokines play in ACAID. IFN-γ production in draining lymph nodes induced by conventional immunization with protein Ag and adjuvant was suppressed after intraocular injection of protein Ag administered either before or after sensitization; IL-12 production in these mice was not decreased, suggesting that suppression of IL-12 may not be the mechanism involved in the impairment in IFN-γ production. Surprisingly, although significant amounts of IL-4 (but not IL-10) were produced by spleen and lymph node cells from several different strains of mice, experiments in IL-4 knockout mice showed that impairment of neither DH nor IFN-γ production required IL-4. Interestingly, significant levels of TGF-β were detected in cultures of spleen cells from mice with ACAID. As determined by quantitative RT-PCR, TGF-β was produced primarily by the splenic CD4 and non-T cells and was of the TGF-β1 type. These results suggest that the Th1 response is impaired in ACAID by a mechanism(s) that does not require Th2-type cytokines, but may involve TGF-β at several different (including the effector) phases during the response.