LIGATION OF CD4 CONCOMITANT TO ACTIVATION INDUCES PRIMARY CD4(-CELL ADHESION AND PSEUDOPODIA FORMATION IN-VITRO() T)

A regulatory function for CD4 molecules in lymphocyte adhesion and mot ility was investigated. Murine splenic CD4(+) T cells, activated in th e presence of phorbol ester and immobilized anti-CD4 mAb, adhered to t he plastic surface and formed extended cytoplasmic projections (pseudo podia). Pseudopod formation was cell-density-dependent, peaked at Day 3, and disappeared by Day 5 in culture. This response could be inhibit ed by soluble anti-CD4 and by RGD-containing peptide. Ligation of CD4 was required at a late stage in cell activation, and stimulated cell m otility in vitro. Addition of IL-4, but not IL-2, upregulated pseudopo d formation induced by suboptimal stimuli. Anti-IL-4 mAb blocked pseud opod formation, and exogenous IL-4 restored the response. A combinatio n of IL-4 plus phorbol ester, but not IL-2 plus phorbol ester, induced pseudopod formation in concert with CD4 ligation. Exogenous IL-2, on the other hand, blocked pseudopod formation. CD45RB(low) CD4(+) T cell s were much more efficient than CD45RB(high) CD4(+) T cells for pseudo pod formation. These results indicate that CD4 ligation induces CD4(+) T-cell adhesion and motility, mainly in the memory/activated subset, which might be relevant for immune responses in vivo. (C) 1996 Academi c Press, Inc