Requirement for p56(lck) tyrosine kinase activation in Th subset differentiation.
The lymphocyte-specific protein tyrosine kinase p56(lck) (Lck) is well documented with regard to its role in regulating T cell activation and thymocyte development through delivery of signals via the mature alphabeta TCR as well as the pre-TCR. Little is known, however, about the role of Lck in Th cell subset differentiation in the periphery. Here, we assess the requirement for tyrosine kinase activation of Lck in Th1 and Th2 cell differentiation by using a dominant-negative Lck (DLGKR) transgenic (Tg) mice under the control of a lck distal promoter that directs high expression in mature T cells, in which splenic CD4 T cells developed normally. This Tg mouse provides a good experimental model system to investigate the roles of Lck in mature T cell function in vivo. We show that the catalytically inactive Lck protein at about twice-normal concentrations inhibits Th2 subset differentiation in vivo and in vitro, whilst leaving the maturation of the other T cell subset, Th1, intact. These data indicate a requirement for Lck activity in Th2 cell differentiation, and a differential dependence for Lck activity between Th2 and Th1 cell differentiation.
Yamashita
M
M
Research Institute for Biological Sciences, Science University of Tokyo, Noda City, Chiba, Japan.
Hashimoto
K
K
Kimura
M
M
Kubo
M
M
Tada
T
T
Nakayama
T
T
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000917:Antibody Formation; D015704:CD4 Antigens / Q000276:immunology; D002454:Cell Differentiation; D016207:Cytokines / Q000096:biosynthesis; D004789:Enzyme Activation; D015870:Gene Expression; D006579:Heterozygote; D008213:Lymphocyte Activation; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010047:Ovalbumin / Q000737:chemistry / Q000276:immunology; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D018417:Th1 Cells / Q000166:cytology / Q000201:enzymology* / Q000276:immunology; D018418:Th2 Cells / Q000166:cytology / Q000201:enzymology* / Q000276:immunology
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D016207:Cytokines; D011948:Receptors, Antigen, T-Cell; D010047:Ovalbumin; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)