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Involvement of the CD4 molecule in a post‐activation event on T cell proliferation

Abstract:

A monoclonal antibody (mAb) directed to a human leukocyte 55‐kDa cell surface molecule with identical cellular distribution and biochemical properties to the CD4 was able to inhibit T cell proliferation induced either in a mixed lymphocyte culture or by activation with mAb anti‐CD3, anti‐CD2 or phytohemagglutinin. The inhibitory effect of anti‐CD4 was observed in the absence of monocytes and was directly exerted on T4+ cells. This effect on cellular proliferation appears to be due to an inhibition of a post‐activation event since (a) the rise of cytoplasmic Ca2+ after activation with anti‐CD3 mAb is not affected by the presence of anti‐CD4 and (b) the proliferation that occurs after an activation pulse of 3 h with ionophore and phorbol myristate acetate can be inhibited when the anti‐CD4 is added after the pulse period. Kinetic studies demonstrated that the inhibition of cellular proliferation by anti‐CD4 mAb was observed even if the antibody was added as late as 18–24 h after the initiation of the culture. The effect of this blocking anti‐CD4 mAb on the interleukin (IL) 2/IL 2 receptor signalling pathways was also examined. The presence of anti‐CD4 slightly affected the production of IL 2. In fact, addition of exogenous recombinant IL 2 at the initiation of the cultures did not restore the proliferative response. However, anti‐CD4 had a strong inhibitory effect on the expression of IL 2 receptors as analyzed by direct immunofluorescence cytometry. Taken together, these results indicate that the binding of the anti‐CD4 mAb to T cells interferes with a late metabolic step being capable of abolishing the proliferative activity of fully activated cells. Copyright © 1987 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim