CUTTING EDGE - CONSTITUTIVE ACTIVATION OF TCR SIGNALING MOLECULES IN IL-2-INDEPENDENT HERPESVIRUS SAIMIRI-TRANSFORMED T-CELLS

Both human T cell leukemia virus type I and simian Herpes-virus saimir i (HVS) transform human T cells in vitro. Although IL-2-independent gr owth in human T cell leukemia virus type I-transformed T cells is asso ciated with constitutive phosphorylation of JAK/STAT kinases, we now d emonstrate that different mechanisms may be responsible for the abilit y of HVS-transformed T cells to proliferate in the absence of exogenou s cytokines. The IL-2 independence of an HVS-transformed cell line cor related with constitutive activation of protein tyrosine kinases known to be induced following TCR engagement. Thus, in these cells we obser ved increased phosphotransferase activity of Lck as well as constituti ve tyrosine phosphorylation of the TCR-associated ZAP-70 kinase and ex pression of the related Syk protein tyrosine kinase. While Syk is gene rally not expressed in activated T cells, its introduction has been sh own to enhance TCR responsiveness. These results suggest that distinct signal transduction cascades can participate in the transition of T c ells to IL-2 independence.