IL-4 enhances IL-10 gene expression in murine Th2 cells in the absence of TCR engagement.
Both IL-4 and IL-10 are regulatory cytokines produced by Th2 cells that can down-regulate cell-mediated immune responses. The studies reported here examine the influence of various cytokines in the regulation of T cell IL-10 production. The results indicate that IL-10 gene expression by TCR transgenic Th2 cells is significantly up-regulated by IL-4 in the absence of TCR signals. IL-4 enhances both IL-10 mRNA levels and secreted protein, and this effect is not related to enhanced mRNA stability. TCR-mediated IL-10 gene expression is inhibited by cyclosporin A, but IL-4-mediated IL-10 expression is not. IL-4 also enhances IL-13 mRNA levels, to a lesser extent than IL-10, but does not significantly effect the expression of other cytokine mRNAs. Furthermore, IL-4 does not significantly enhance IL-10 expression in Th1 cells. IL-2 also enhances effector cytokine production in the absence of TCR signals, but in a subset nonspecific manner, increasing both Th2 IL-4 mRNA and Th1 IFN-gamma mRNA. These data suggest that Th2 IL-4 production may contribute to the down-regulation of immune responses by directly enhancing Th2 IL-10 production. In addition, the data clearly demonstrate that exogenous cytokines can significantly influence effector cytokine production by effector T cells without the requirement for TCR signals.
Schmidt-Weber
C B
CB
Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Alexander
S I
SI
Henault
L E
LE
James
L
L
Lichtman
A H
AH
D000276:Adjuvants, Immunologic / Q000502:physiology*; D000818:Animals; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology*; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics*; D007376:Interleukin-2 / Q000502:physiology; D015847:Interleukin-4 / Q000502:physiology*; D053614:Janus Kinase 2; D051379:Mice; D008806:Mice, Inbred AKR; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D018417:Th1 Cells / Q000201:enzymology / Q000378:metabolism; D018418:Th2 Cells / Q000201:enzymology / Q000378:metabolism*; D020032:Tyrphostins / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics / Q000276:immunology
D000276:Adjuvants, Immunologic; D007376:Interleukin-2; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; D016753:Interleukin-10; D015847:Interleukin-4; D016572:Cyclosporine; D011505:Protein-Tyrosine Kinases; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2