The role of p56lck in the development of gamma delta T cells and their function during an infection by Listeria monocytogenes.

We investigated roles of p56lck tyrosine kinase (Lck) on the development and function of gamma delta T cells in adult mice using lck gene knockout (lck -/-) mice. The mature gamma delta T cells (heat-stable Ag negative) were generated significantly in the thymi of adult lck -/- mice. When Listeria monocytogenes was infected i.p., gamma delta T cells were induced in the peritoneal cavity of the lck -/- mice. Interestingly, the repertoire of gamma delta T cells was obviously different in the lck +/+ and lck -/- mice; i.e., the gamma delta T cells of the lck -/- mice induced by the listerial infection dominantly expressed V delta 1 while those of the lck +/+ mice dominantly expressed V delta 6. The V delta 1 + gamma delta T cells in the lck -/- mice were extrathymically generated, supported by their appearance in thymectomized irradiated mice reconstituted with bone marrow cells from the lck -/- mice. Furthermore, the gamma delta T cells of the lck +/+ mice were protective in the early stage of the listerial infection, while the gamma delta T cells in the lck -/- mice were not protective against the listerial infection because the depletion of the gamma delta T cells from the lck -/- mice did not influence the bacterial burden in the spleens. These observations thus suggest that 1) gamma delta T cells can develop in adult mice through the intrathymic and extrathymic pathways even in the absence of Lck, 2) Lck influences the expansion and the repertoire of gamma delta T cells, and 3) the gamma delta T cells raised in the absence of Lck are not protective against L. monocytogenes.