Interleukin-4 acts at the locus of the antigen-presenting dendritic cell to counter-regulate cytotoxic CD8+T-cell responses

The mechanism underlying suppression of immune responses by interleukin-4 ( IL-4) has remained unexplained. Here we show that the antigen-presenting de ndritic cell Is central to counter-regulation of autoimmune disease by IL-4 . IL-4 acts at the locus of the dendritic cell to decrease the cytolytic T- cell response, preventing autoimmunity. Stimulation of cytotoxic precursors by antigen pulsed dendritic cells induces their differentiation but the pr ocess is blocked by IL-4. IL-40-influenced DC produce distinct effects on C D8(+) T cells depending on their state of activation. The molecular basis f or this regulation is the alteration of the expression ratio of the costimu latory ligands B7.1/B7.2 on dendritic cells. Our findings demonstrate that B7.2 induces expansion of CD8(+) T cells and B7.1 governs their acquisition of cytolytic activity. IL-4 influences the dendritic cell to elicit qualit ative differences in T-cell responses, providing the basis for counter-regu lation mediated by IL-4.