Requirement for tyrosine kinase p56ick for thymic development of transgenic gamma delta T cells

The Src-related protein tyrosine kinase [p56.sup.lck] 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 [p56.sup.lck] in the development of T cells that have γδ TCRs, which generally do not express CD4 or CD8, [p56.sup.lck] mutant mice were bred with TCRγδ transgenic mice. Few peripheral cells that carried the transgenes could be detected in [p56.sup.lck-/-] mice, although 70 percent of thymocytes were transgenic. Development of transgenic γ[delta.sup.+] thymocytes was blocked at an early stage, defined by interleukin-2 receptor α expression. However, extrathymic development of [CD8αα.sup.+] [TCRγδ.sup.+] intestinal intraepithelial lymphocytes appeared to be normal. Thus, [p56.sup.lck] is crucial for the thymic, but not intestinal, maturation of γδ T cells and may function in thymic development independently of CD4 or CD8.
The molecular requirements for the development of [TCRγδ.sup.+] lymphocytes are poorly characterized[1]. Thymic development of TCRαβ cells unfolds in stages defined by expression of CD4 and CD8[2]. Early [CD4.sup.-][CD8.sup.-] precursors [...]