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• W2071733190 abstract "The actions of a humanised therapeutic CD4 mAb YHB.46 on T cell activation were investigatedin vitro.Soluble YHB.46 IgG or YHB.46-derived F(ab′)2fragments caused inhibitions of up to 100% of the proliferation of purified CD4+T cells activated with immobilised CD3 mAb. The inhibitory effects of the CD4 mAb were equally potent in both CD45RA+and CD45RO+T cell subset proliferation assays. Inhibitory effects on DNA synthesis were not explicable by increased T cell apoptosis. YHB.46 was inhibitory even when added 70 h after exposure of cells to immobilised CD3 mAb, but it had little effect on IL-2 receptor-driven proliferation signals. The CD4 mAb inhibited the CD3-induced expression of the CD25 and CD69 activation markers on the T cell surface and suppressed CD40 ligand expression, but not that of CD25 and CD69, when their expression was induced by phorbol ester plus ionomycin. YHB.46 also exerted a profound inhibitory effect on the production of IL-2, IL-4, and IL-10, irrespective of whether T cells were activated with CD3 mAb or with phorbol ester plus ionomycin. The inhibitory effects of YHB.46 on CD4+T cell proliferation were partially prevented by the addition of exogenous IL-2 or autologous monocytes and were completely prevented by activating T cells with a novel CD3–CD28 bivalent F(ab′)2reagent. However, the inhibitory effects of YHB.46 on T cell proliferation were equipotent in the presence or the absence of CTLA-4Ig, showing that the CD4 mAb was not acting on CD28-induced activation signals per se. Our results show that the inhibitory effects of YHB.46 on T cell activation do not involve CD28 or IL-2 receptor signalling, but are directed at the TCR-mediated G0-G1 transition. These findingsin vitropredict that YHB.46 may act as a potent immunosuppressant in the clinical context." @default.
• W2071733190 created "2016-06-24" @default.
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• W2071733190 date "1998-05-01" @default.
• W2071733190 modified "2023-10-01" @default.
• W2071733190 title "A Humanised Therapeutic CD4 mAb Inhibits TCR-Induced IL-2, IL-4, and IL-10 Secretion and Expression of CD25, CD40L, and CD69" @default.
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• W2071733190 doi "https://doi.org/10.1006/cimm.1998.1287" @default.
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