Requirement for tyrosine kinase p56^lck for thymic development of transgenic γδ T cells

Abstract

The Src-related protein tyrosine kinase p56lck is essential for antigen-specific signal transduction and thymic maturation of T cells that have an αβ 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 γδ TCRs, which generally do not express CD4 or CD8, p56lck mutant mice were bred with TCRγδ 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 γδ + thymocytes was blocked at an early stage, defined by interleukin-2 receptor α expression. However, extrathymic development of CD8αα+TCRγδ+ intestinal intraepithelial lymphocytes appeared to be normal. Thus, p56lck is crucial for the thymic, but not intestinal, maturation of γδ T cells and may function in thymic development independently of CD4 or CD8.