DISTINCT ISOFORMS OF THE CD45 PROTEIN-TYROSINE-PHOSPHATASE DIFFERENTIALLY REGULATE INTERLEUKIN-2 SECRETION AND ACTIVATION SIGNAL PATHWAYS INVOLVING VAV IN T-CELLS

The CD45 family of transmembrane protein-tyrosine phosphatases plays a crucial role in the regulation of lymphocyte activation by coupling a ctivation signals from antigen receptors to the signal transduction ap paratus. Multiple CD45 isoforms, generated through regulated alternati ve mRNA splicing, differ only in the length and glycosylation of their extracellular domains. Differential distribution of these isoforms de fines subsets of T cells having distinct functions and activation requ irements, While the requirement for the intracellular protein-tyrosine phosphatase domains has been documented, the physiological role of th e extracellular domains remains elusive. Here we report the generation of CD45-antisense transfected Jurkat T cell clones that lack CD45 or have been reconstituted to uniquely express either the smallest, CD45( 0), or the largest, CD45(ABC), isoform. These cells exhibited marked i soform-dependent differences in IL-2 production and tyrosine phosphory lation of cellular proteins, including Vav after anti-CD3 stimulation. These results demonstrate that the distinct CD45 extracellular domain s differentially regulate T cell receptor-mediated signaling pathways. Furthermore, these findings suggest that alterations in CD45 isoform expression by individual T cells during thymic ontogeny and after anti gen exposure in the periphery directly affects the signaling pathways utilized.