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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.
M Yamashita, and
K Hashimoto, and
M Kimura, and
M Kubo, and
T Tada, and
T Nakayama
April 1999,
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M Yamashita, and
K Hashimoto, and
M Kimura, and
M Kubo, and
T Tada, and
T Nakayama
March 2001,
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M Yamashita, and
K Hashimoto, and
M Kimura, and
M Kubo, and
T Tada, and
T Nakayama
May 2004,
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M Yamashita, and
K Hashimoto, and
M Kimura, and
M Kubo, and
T Tada, and
T Nakayama
May 1997,
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M Yamashita, and
K Hashimoto, and
M Kimura, and
M Kubo, and
T Tada, and
T Nakayama
March 2001,
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M Yamashita, and
K Hashimoto, and
M Kimura, and
M Kubo, and
T Tada, and
T Nakayama
September 1996,
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M Yamashita, and
K Hashimoto, and
M Kimura, and
M Kubo, and
T Tada, and
T Nakayama
December 1996,
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M Yamashita, and
K Hashimoto, and
M Kimura, and
M Kubo, and
T Tada, and
T Nakayama
August 2004,
International immunology,
M Yamashita, and
K Hashimoto, and
M Kimura, and
M Kubo, and
T Tada, and
T Nakayama
March 1997,
FEBS letters,
M Yamashita, and
K Hashimoto, and
M Kimura, and
M Kubo, and
T Tada, and
T Nakayama
August 2000,
Molecular immunology,
