DIFFERENTIAL CD4-DEPENDENT REGULATION OF NAIVE AND MEMORY CD4(+) T-CELL ADHESION IS NOT RELATED TO DIFFERENCES IN EXPRESSION AND FUNCTION OF CD4 AND P56(LCK)

We have previously reported that antigen-independent adhesion of CD45RO(+) memory CD4(+) T cells to B cells is negatively regulated by CD4 - MHC class II interaction, whereas that of CD45RA(+) naive CD4(+) T cells is not. We have now found that both cross-linking of CD4 ligands [anti-CD4 mAbs, HIV gp160 (env) protein and a 12mer peptide encompassing the 35 - 46 sequence of the HLA-DR beta 1 domain] on CD4(+) naive T cells and activation-induced conversion of naive CD4(+) T cells to memory T cells leads to CD4-dependent down-regulation of adhesion. To further elucidate CD4-dependent differential regulation of naive and memory T cell adhesion to a cells, we investigated the expression and function of CD4 and p56(lck), a tyrosine kinase associated with the cytoplasmic domain of CD4. p56(lck) tyrosine kinase activity was equally enhanced by anti-CD4 mAbs and gp160 (120) in the two subsets. Furthermore, cell-surface CD4 down-modulation by phorbol myristate acetate or anti-CD4 mAbs was similar in the two subsets, which express the same amounts of both cell-surface CD4 and CD4-associated p56(lck). Finally, the pattern of tyrosine phosphorylation of cellular proteins induced by gp120 (160) was similar in the two subsets. Taken together, these results indicate that the different sensitivity of naive and memory CD4(+) T cells to CD4-dependent regulation of adhesion is not accounted for by differences in the tyrosine kinase activity of p56(lck); it probably, therefore, involves a step downstream of p56(lck) or another pathway differentially used in naive and memory CD4(+) T cells.