HUMAN CD4 CD45RA+ AND CD4/CD45RA- T-CELL SUBSETS EXPRESS CD4-P56(LCK)COMPLEXES, CD4-ASSOCIATED LIPID KINASES, TCR/CD3-P59(FYN) COMPLEXES, AND SHARE SIMILAR TYROSINE KINASE SUBSTRATES/

T cell activation appears to be regulated by an interplay between prot ein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPases ). p56lck and p59fyn have been found to associate with CD4 and TCR - C D3 respectively. The CD45 family of transmembrane PTPases has been sho wn to be able to regulate the activities of these receptor-associated PTKs in vitro. In man, CD45 contains five different isoforms whose dis tribution defines subsets of T cells having distinct activation requir ements and in vitro functions. Several groups have reported a physical interaction between distinct isoforms of CD45 and CD2, CD4, and the T CR - CD3 complex. Given the potential regulatory interaction between C D45 and PTKs in CD4+ subsets expressing different CD45 isoforms, we ha ve examined CD4 associated and TCR - CD3- associated PTK activities, a ssociated phosphatidyl inositol (PI) kinases and substrates of tyrosin e phosphorylation in CD45RA+ and CD45RA- CD4+ T cell lines derived fro m peripheral blood. Both subsets express CD4-associated p56lck and TCR - CD3-associated p59fyn kinases which exhibit identical in vitro phos phorylation at the Y-394 and Y-420 autophosphorylation sites respectiv ely. Further, both subsets exhibited PI kinases activity associated wi th CD4-p56lck. Consistent with these observations, anti-CD3 crosslinki ng induced the phosphorylation of a similar spectrum of intracellular substrates in these CD45RA+ and CD45RA- CD4+ T cell lines. These obser vations indicate that despite the possible interaction between CD45 is oforms and CD4 or TCR - CD3, the mere expression of the CD45RA isoform does not in and of itself alter the presence of receptor-associated k inases or their intracellular targets.