Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

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.

Original publication

DOI

10.1006/cimm.1998.1287

Type

Journal article

Journal

Cell Immunol

Publication Date

01/05/1998

Volume

185

Pages

101 - 113

Keywords

Animals, Antibodies, Monoclonal, Antigens, CD, Antigens, Differentiation, T-Lymphocyte, Binding Sites, Antibody, Binding, Competitive, CD28 Antigens, CD3 Complex, CD4 Antigens, CD4-Positive T-Lymphocytes, CD40 Antigens, CD40 Ligand, Cytokines, Humans, Immunosuppressive Agents, Interleukin-10, Interleukin-2, Interleukin-4, Interleukins, Lectins, C-Type, Ligands, Lymphocyte Activation, Membrane Glycoproteins, Membrane Proteins, Mice, Muromonab-CD3, Phosphorylation, Receptors, Antigen, T-Cell, Receptors, Fc, Receptors, Interleukin-2, Tyrosine, Up-Regulation