Uveitogenicity Is Associated with a Th1-like Lymphokine Profile: Cytokine-Dependent Modulation of Early and Committed Effector T Cells in Experimental Autoimmune Uveitis

Abstract

This study addresses the nature of the pathogenic effector T cell in experimental autoimmune uveoretinitis and the effect of different cytokines on these cellsin vitro.Lymph node cells of B10.RIII mice immunized with the uveitogenic peptide 161-180 of interphotoreceptor retinoid binding protein were cultured with the peptide with or without IL-12, IL-4, or anti-IL-4. An antigen-specific T cell line was subsequently derived from these cells. Primary cultures of immune lymph node cells stimulated with the peptide proliferated and produced IL-2 and some IL-4, but no IFN-γ. The addition of recombinant IL-12 resulted in abundant production of IFN-γ, which was blocked by the addition of IL-4 and was enhanced by anti-IL-4. Only those cultures that produced IFN-γin vitrowere uveitogenicin vivo.A long-term uveitogenic T cell line, initially derived in the presence of IL-12, produced IFN-γ and IL-2, but not IL-4, and was CD4⁺(Th1-like). Antigen-specific proliferation and IFN-γ production of the line were enhanced by exogenous IL-4, TGF-β, IL-2, IL-6, IL-7, and IL-9 and were inhibited by IL-10 and TNF-α. Our results provide support for the hypothesis that the uveitogenic effector T cell has a Th1-like phenotype. Furthermore, the data suggest that the effects of the cytokine milieu on fully differentiated Th1 effectors may differ considerably from their effects on less mature stages of antigen-specific T cells.