REQUIREMENT FOR TYROSINE KINASE P56(LCK) FOR THYMIC DEVELOPMENT OF TRANSGENIC GAMMA-DELTA-T-CELLS

The Src-related protein tyrosine kinase p56lck is essential for antigen-specific signal transduction and thymic maturation of T cells that have an alphabeta T cell receptor (TCR), presumably by physical association with CD4 or CD8 molecules. To evaluate the requirement for p56lck in the development of T cells that have gammadelta TCRs, which generally do not express CD4 or CDB, p56lck mutant mice were bred with TCRgammadelta transgenic mice. Few peripheral cells that carried the transgenes could be detected in p56lck-/- mice, although 70 percent of thymocytes were transgenic. Development of transgenic gammadelta+ thymocytes was blocked at an early stage, defined by interleukin-2 receptor alpha expression. However, extrathymic development of CD8alphaalpha+TCR-gammadelta+ intestinal intraepithelial lymphocytes appeared to be normal. Thus, p56lck is crucial for the thymic, but not intestinal, maturation of gammadelta T cells and may function in thymic development independently of CD4 or CD8.