A cascade of cytokines is responsible for IL-9 expression in human T cells. Involvement of IL-2, IL-4, and IL-10.
We have previously demonstrated that IL-9 induction in human T cells stimulated with PMA and anti-CD3 Ab is mediated by IL-2, as it was blocked by anti-IL-2R Ab. The experiments reported here indicate that anti-IL-2R Ab also inhibited the expression of IL-4, IL-6, and IL-10, thereby raising the possibility that the blockade of IL-9 production by anti-IL-2R mAb could be secondary to the blockade of these cytokines. We found that the inhibition caused by anti-IL-2R Ab on IL-9 production could be reversed by the addition of a combination of IL-4 and IL-10. Moreover, IL-9 production by T cells stimulated with PMA and anti-CD3 Ab was blocked by the addition of anti-IL-4 and anti-IL-10 Abs. Similar results were obtained with T cells cultured on B7-1/Fc gamma RII-transfected fibroblasts in the presence of anti-CD3 Ab. Analysis of cytokine production by different T cell subsets revealed that IL-4, IL-9, and IL-10 were produced only by CD45 Ro+ T cells. Importantly, CD45 Ra+ T cells were capable of producing IL-9 provided that both IL-4 and IL-10 were added to the cultures. The possible relationship between IL-4 production and IL-10 production was clarified by experiments indicating that IL-10 production was inhibited by anti-IL-4 Ab. However, IL-4 was not sufficient to trigger IL-10 production, which required both IL-2 and IL-4. Taken together, our results demonstrate the existence of a cascade of cytokines responsible for IL-9 expression, with IL-2 being required for IL-4 production, a combination of IL-2 and IL-4 for IL-10 production, and a combination of IL-4 and IL-10 for IL-9 production. Kinetics studies of cytokine gene expression in T cells further validated this model.
Houssiau
F A
FA
Rheumatology Unit, Catholic University of Louvain, Brussels, Belgium.
Schandené
L
L
Stevens
M
M
Cambiaso
C
C
Goldman
M
M
van Snick
J
J
Renauld
J C
JC
D000911:Antibodies, Monoclonal / Q000276:immunology; D001483:Base Sequence; D006801:Humans; D066298:In Vitro Techniques; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D015847:Interleukin-4 / Q000096:biosynthesis / Q000276:immunology; D016906:Interleukin-9 / Q000096:biosynthesis*; D007378:Interleukins / Q000096:biosynthesis / Q000276:immunology*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D015375:Receptors, Interleukin-2 / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D007376:Interleukin-2; D016906:Interleukin-9; D007378:Interleukins; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D016753:Interleukin-10; D015847:Interleukin-4