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• W4313305990 endingPage "7119" @default.
• W4313305990 startingPage "7110" @default.
• W4313305990 abstract "Abstract T cell proliferation and cytokine production usually require stimulation via both the TCR/CD3 complex and the CD28 costimulatory receptor. Using purified human CD4+ peripheral blood T cells, we show that CD28 stimulation alone activates p38α mitogen-activated protein kinase (p38α). Cell proliferation induced by CD28 stimulation alone, a response attributed to CD4+CD45RO+ memory T cells, was blocked by the highly specific p38 inhibitors SB 203580 (IC50 = 10–80 nM) and RWJ 67657 (IC50 = 0.5–4 nM). In contrast, proliferation induced by anti-CD3 plus anti-CD28 mAbs was not blocked. Inhibitors of p38 also blocked CD4+ T cell production of IL-4 (SB 203580 IC50 = 20–100 nM), but not IL-2, in response to CD3 and CD28 stimulation. IL-5, TNF-α, and IFN-γ production were also inhibited, but to a lesser degree than IL-4. IL-4 production was attributed to CD4+CD45RO+ T cells, and its induction was suppressed by p38 inhibitors at the mRNA level. In polarized Th1 and Th2 cell lines, SB 203580 strongly inhibited IL-4 production by Th2 cells (IC50 = 10–80 nM), but only partially inhibited IFN-γ and IL-2 production by Th1 cells (&lt;50% inhibition at 1 μM). In both Th1 and Th2 cells, CD28 signaling activated p38α and was required for cytokine production. These results show that p38α plays an important role in some, but not all, CD28-dependent cellular responses. Its preferential involvement in IL-4 production by CD4+CD45RO+ T cells and Th2 effector cells suggests that p38α may be important in the generation of Th2-type responses in humans." @default.
• W4313305990 created "2023-01-06" @default.
• W4313305990 creator A5017572254 @default.
• W4313305990 creator A5034806661 @default.
• W4313305990 creator A5038836186 @default.
• W4313305990 creator A5063761193 @default.
• W4313305990 date "1999-06-15" @default.
• W4313305990 modified "2023-10-18" @default.
• W4313305990 title "p38α Mitogen-Activated Protein Kinase Is Activated by CD28-Mediated Signaling and Is Required for IL-4 Production by Human CD4+CD45RO+ T Cells and Th2 Effector Cells" @default.
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• W4313305990 doi "https://doi.org/10.4049/jimmunol.162.12.7110" @default.
• W4313305990 hasPublicationYear "1999" @default.
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