The Journal of Immunology, Vol 156, Issue 5 1818-1823, Copyright © 1996 by American Association of Immunologists

ARTICLES

Human IL-13 production is negatively influenced by CD3 engagement. Enhancement of IL-13 production by cyclosporin A

TC van der Pouw Kraan, LC Boeije, JT Troon, SK Rutschmann, J Wijdenes and LA Aarden
Department of Autoimmune Diseases, Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam.

IL-13, a T cell-derived cytokine, shares many of its biologic activities with the Th2 cytokine IL-4, including induction of a class switch to IgE and anti-inflammatory properties. Its potential impact on development of Th2 responses makes it interesting to determine how the production of IL-13 is regulated and which cell types produce IL-13. In this work, we show that IL-13 is produced optimally by T cells when stimulated with a combination of anti-CD28 and PMA. Unexpectedly, additional ligation of the TCR complex with Abs to CD3 caused an approximately fivefold inhibition of IL-13 production. Moreover, this inhibition could be reversed by cyclosporin A (CsA). The effect of CsA did not depend on the presence of PMA; upon CD3 and CD28 stimulation, CsA equally enhanced 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 mainly in CD4+ memory cells, required costimulation through CD3, and was 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.

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