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.
Fujise
S
S
Department of Immunology, Medical Institute of Bioregulation, Kyusyu University, Fukuoka, Japan.
Matsuzaki
G
G
Kishihara
K
K
Kadena
T
T
Molina
T
T
Nomoto
K
K
D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000276:immunology; D005260:Female; D008088:Listeriosis / Q000276:immunology* / Q000378:metabolism; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D009928:Organ Specificity / Q000276:immunology; D010529:Peritoneal Cavity / Q000166:cytology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis / Q000096:biosynthesis; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000201:enzymology* / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology; D019061:src-Family Kinases / Q000276:immunology* / Q000502:physiology*
D016692:Receptors, Antigen, T-Cell, gamma-delta; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D019061:src-Family Kinases