T-CELL ACTIVATION THROUGH THY-1 IS ASSOCIATED WITH THE EXPRESSION OF A SURFACE PROTEIN (P100) ON A SUBSET OF CD4 CELLS

Thy-1 molecules, which lack a transmembrane domain, can nonetheless in duce T cell activation; it has thus been suggested that a separate tra nsmembrane molecule associated with Thy-1 is required for signal trans duction. We have previously characterized a transmembrane protein with an M(r) of 100,000 (p100), which is non-covalently bound to two glyco syl-phosphatidylinositol (GPI)-linked molecules, Thy-1 and ThB. p100 i s selectively expressed on the T cell surface and divides peripheral C D4 cells into two subpopulations. This differential expression on CD4 cells allowed us to investigate the role of p100 in signal transductio n through Thy-1 molecules. Here we report that only p100(+) CD4 cells proliferate and release cytokines in response to cross-linkage of Thy- 1, although both p100(+) and p100(-) CD4 cells strongly express Thy-1 on their surfaces. Control stimulation by anti-CD3 antibodies or conca navalin A induces identical thymidine uptake by the two CD4 cell popul ations. Interestingly, these two populations of CD4 cells had differen t cytokine release profiles after activation through CD3: only p100(+) CD4 cells released high amounts of IL-2 and IFN-gamma, whereas both p opulations released IL-4. p100 expression correlates with the inductio n of homotypic aggregation of T cells after Thy-1 triggering. p100 is associated with kinase activity (fyn and lck), and phosphorylated prot eins of 90, 59, 57 and 33 kDa co-precipitate with Thy-1 only in p100() CD4 cells. Altogether, these data suggest that p100 is involved in s ignal transduction through Thy-1. p100 expression by activated CD4 cel ls in vive may be relevant to the proposed function of Thy-1 as an acc essory signaling molecule in cell activation.