UVEITOGENICITY IS ASSOCIATED WITH A TH1-LIKE LYMPHOKINE PROFILE - CYTOKINE-DEPENDENT MODULATION OF EARLY AND COMMITTED EFFECTOR T-CELLS IN EXPERIMENTAL AUTOIMMUNE UVEITIS

This study addresses the nature of the pathogenic effector T cell in e xperimental autoimmune uveoretinitis and the effect of different cytok ines on these cells in vitro. Lymph node cells of B10.RIII mice immuni zed with the uveitogenic peptide 161-180 of interphotoreceptor retinoi d 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 I L-4, but no IFN-gamma. The addition of recombinant IL-12 resulted in a bundant production of IFN-gamma, which was blocked by the addition of IL-4 and was enhanced by anti-IL-4. Only those cultures that produced IFN-gamma in vitro were uveitogenic in vivo. A long-term uveitogenic T cell line, initially derived in the presence of IL-12, produced IFN-g amma and IL-2, but not IL-4, and was CD4(+) (Th1-like). Antigen-specif ic proliferation and IFN-gamma production of the line were enhanced by exogenous IL-4, TGF-beta, IL-2, IL-6, IL-7, and IL-9 and were inhibit ed by IL-10 and TNF-alpha. Our results provide support for the hypothe sis that the uveitogenic effector T cell has a Th1-like phenotype. Fur thermore, the data suggest that the effects of the cytokine milieu on fully differentiated Th1 effecters may differ considerably from their effects on less mature stages of antigen-specific T cells.