Human IL-13 production is negatively influenced by CD3 engagement. Enhancement of IL-13 production by cyclosporin A.
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.
van der Pouw Kraan
T C
TC
Department of Autoimmune Diseases, Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam.
Boeije
L C
LC
Troon
J T
JT
Rutschmann
S K
SK
Wijdenes
J
J
Aarden
L A
LA
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D018106:CD28 Antigens / Q000276:immunology; D017252:CD3 Complex / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D018793:Interleukin-13 / Q000096:biosynthesis*; D051379:Mice; D008807:Mice, Inbred BALB C; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000276:immunology
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D018106:CD28 Antigens; D017252:CD3 Complex; D018793:Interleukin-13; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D016572:Cyclosporine