ENGAGEMENT OF THE COMMON LEUKOCYTE ANTIGEN CD45 INDUCES HOMOTYPIC ADHESION OF ACTIVATED HUMAN T-CELLS

The transmembrane tyrosine phosphatase CD45 plays an important role in TCR/CD3-mediated signaling. We demonstrate in this study that ligand binding to the CD45 molecule induces homotypic cell adhesion of activa ted, but not resting, T lymphocytes. mAbs to CD45 (4B2 and 10C10) and to CD45RO (UCHL1), but not to CD45RA (IOL2), caused sustained adhesion of alloreactive T cell lines. In contrast, none of the anti-CD45 mAbs induced aggregation of resting peripheral T cells. CD45-mediated adhe sion of activated T cells involved both CD11a/18-dependent as well as CD11a/ 18-independent mechanisms. mAb 4B2 induced a strictly CD11a/18- dependent adhesion that was completely inhibited by both the protein k inase C (PKC) inhibitor sphingosine and the protein tyrosine kinase (P TK) inhibitors genestein and herbimycin A. In contrast, mAb 10C10, whi ch recognized an epitope on CD45 distinct from the one recognized by m Ab 4B2, induced CD11a/18-independent adhesion that was inhibited by sp hingosine, but not by genestein or herbimycin A, Biochemical studies r evealed direct evidence For activation of protein kinase C and protein tyrosine kinase after engagement of CD45 on activated T cells by mAb 4B2. These results indicate that in addition to its role in TCR/CD3-me diated activation, engagement of CD45 transduces signals that result i n enhanced adhesiveness of activated T cells.