Regulation of LFA‐1‐mediated T cell adhesion by CD4

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Abstract
Heterotypic adhesion of T lymphocytes to monocytes. B lymphocytes, or other target cells is mainly mediated by LFA‐1 and CD2 molecules. Low‐affinity binding of resting T cells can be transiently up‐regulated by cross‐linking of CD3. We have previously found that binding of specific ligands to CD4 can down‐regulate adhesion of resting T cells to B cells. We now show that the enhanced adhesiveness of CD4+ T cells induced by CD3 cross‐linking using plastic‐bound anti‐CD3 antibody can also be inhibited by several CD4 ligands, i.e. anti‐CD4 antibodies, the gp160 env protein of human immunodeficiency virus, as well as by putative CD4 ligands, i.e. synthetic peptides analogous to the gp160‐binding site to CD4 (positions 418–434 and 449‐464) and a 12‐mer synthetic peptide (DR‐12) analogous to positions 35–46 of HLA class II β subunit and including the highly conserved Arg‐Phe‐Asp‐Ser (RFDS) sequence.After CD3 cross‐linking, maximal binding of T cells to HLA class II‐positive and ‐negative B cells was similar, although binding to HLA class II‐negative B cells was more prolonged. T cells that were passively induced to up‐regulate adhesion by binding of a CD11a‐specific antibody, NKIL16, known to enhance LFA‐1‐dependent adhesiveness, were less sensitive to the inhibitory effect of the DR‐12 peptide, whereas the inhibitory effects of gp160 were preserved. The kinetics of adhesion of NKIL16‐pretreated T cells was not influenced by HLA class II expression at the B cell surface. Together, these results strongly suggest that CD4‐HLA class II interaction may down‐regulate low‐affinity adhesion of resting T cells and, to some extent, high‐affinity adhesion of T cells actively induced by CD3 cross‐linking but not passively induced by an anti‐CD11a antibody.

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