A humanised therapeutic CD4 mAb inhibits TCR-induced IL-2, IL-4, and IL-10 secretion and expression of CD25, CD40L, and CD69.

Woods, M; Guy, R; Waldmann, H; Glennie, M; Alexander, DR

Journal article

A humanised therapeutic CD4 mAb inhibits TCR-induced IL-2, IL-4, and IL-10 secretion and expression of CD25, CD40L, and CD69.

Abstract:: The actions of a humanised therapeutic CD4 mAb YHB.46 on T cell activation were investigated in vitro. Soluble YHB.46 IgG or YHB.46-derived F(ab')2 fragments 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 nto 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')2 reagent. 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 findings in vitro predict that YHB.46 may act as a potent immunosuppressant in the clinical context.

Publication status:: Published

Actions

Email

Email this record

Send the bibliographic details of this record to your email address.

Your Email
Please enter the email address that the record information will be sent to.

-
Your message (optional)
Please add any additional information to be included within the email.
Cite

Cite this record

APA Style

Woods, M., Guy, R., Waldmann, H., Glennie, M., & Alexander, D. R. (1998). A humanised therapeutic CD4 mAb inhibits TCR-induced IL-2, IL-4, and IL-10 secretion and expression of CD25, CD40L, and CD69. Cellular Immunology, 185(2), 101–113.

MLA Style

Woods, M., et al. “A Humanised Therapeutic CD4 MAb Inhibits TCR-Induced IL-2, IL-4, and IL-10 Secretion and Expression of CD25, CD40L, and CD69.” Cellular Immunology, vol. 185, no. 2, 1998, pp. 101–13.

Chicago Style

Woods, M, R Guy, H Waldmann, M Glennie, and DR Alexander. 1998. “A Humanised Therapeutic CD4 MAb Inhibits TCR-Induced IL-2, IL-4, and IL-10 Secretion and Expression of CD25, CD40L, and CD69.” Cellular Immunology 185 (2): 101–13.
Share
Print