INHIBITION OF LANGERHANS CELL ANTIGEN-PRESENTING FUNCTION BY IL-10 - A ROLE FOR IL-10 IN INDUCTION OF TOLERANCE

IL-10 is a product of activated keratinocytes and is released during t he induction phase of contact sensitivity. As IL-10 effects have been described as being mediated by APC, we investigated effects of IL-10 o n epidermal Langerhans cells (LC), the resident APC in the epidermis. Initial studies failed to demonstrate effects of IL-10 on MHC class II Ag expression by LC or anti-CD3 mAb- or alloantigen-induced LC-depend ent T cell proliferation. However, production of IFN-gamma and IL-2, ( but not IL-6) was markedly reduced in these assays. When the soluble-p rotein Ag specific T cell clones AE7 (Th1) and D10.G4 (Th2) were subst ituted for unprimed T cells, differential effects of IL-10 on T-cell p roliferation were observed. Whereas IL-10-pretreated and untreated LC supported Th2 cell proliferation equally well, IL-10-pretreated LC wer e essentially unable to induce Th1 cell proliferation in response to n ative protein or peptide Ag. The inhibitory influence of IL-10 on Th1 cells was observed when fresh or 1 day cultured LC were used; 2- or 3- day cultured LC were affected to a much lesser extent by IL-10 pretrea tment. Further, coculture experiments using IL-10-pretreated or untrea ted LC of a different haplotype suggest that IL-10 negatively regulate s a costimulatory signal required for induction of Th1 cell proliferat ion. To assess whether T cells incubated with Ag and IL-10-pretreated LC were responsive to further stimulation, T cells were rescued after 1 day of coculture with IL-10-pretreated LC and restimulated, either i mmediately or after 1 to 5 days of rest, with untreated LC in the pres ence of Ag. T cells incubated with IL-10-pretreated LC were found to b e anergic, whereas T cells incubated with untreated LC proliferated no rmally after further stimulation. However, anergic T cells responded v igorously to IL-2. These data indicate that although IL-10-pretreated LC are effective APC for Th2 cells, they fail to induce Th1 cell proli feration and rather induce clonal anergy in these cells.