HUMAN IL-13 PRODUCTION IS NEGATIVELY INFLUENCED BY CD3 ENGAGEMENT - ENHANCEMENT OF IL-13 PRODUCTION BY CYCLOSPORINE-A

IL-13, a T cell-derived cytokine, shares many of its biologic activiti es with the Th2 cytokine IL-4, including induction of a class switch t o IgE and anti-inflammatory properties, Its potential impact on develo pment of Th2 responses makes it interesting to determine how the produ ction of IL-13 is regulated and which cell types produce IL-13, In thi s work, we show that IL-13 is produced optimally by T cells when stimu lated with a combination of anti-CD28 and PMA. Unexpectedly, additiona l ligation of the TCR complex with Abs to CD3 caused an approximately fivefold inhibition of IL-13 production, Moreover, this inhibition cou ld be reversed by cyclosporin A (CsA), The effect of CsA did not depen d on the presence of PMA; upon CD3 and CD28 stimulation, CsA equally e nhanced IL-13 production, Both naive and memory CD4(+) T cells and CD8 (+) T cells produced IL-13, and production in all cell types could be enhanced by CsA, In contrast to IL-13, IL-4 production was observed ma inly in CD4(+) memory cells, required costimulation through CD3, and w as inhibited by CsA, The unusual regulation and relative abundance of IL-13 make it an important candidate to be controlled tightly by dose and type of TCR ligands. CsA is used widely to inhibit T cell function , The finding that IL-13 production is enhanced instead of diminished in the presence of CsA may explain the Th2-inducing effects of CsA in vivo.