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http://dx.doi.org/10.1007/s10059-009-0121-0

The Effector Functions of Mature T Lymphocytes Are Impaired in Transgenic Mice Expressing the SH2 Domain of TSAd/Lad  

Choi, Youngbong (Department of Life Science, Ewha Womans University)
Park, Eunkyung (Department of Life Science, Ewha Womans University)
Ahn, Eunseon (Department of Life Science, Ewha Womans University)
Park, Inyoung (Department of Life Science, Ewha Womans University)
Yun, Yungdae (Department of Life Science, Ewha Womans University)
Abstract
TSAd/Lad is a T cell adaptor molecule involved in $p56^{lck}$-mediated T cell activation. To investigate the functions of TSAd in T cells, we generated transgenic (TG) mice expressing the SH2 domain of TSAd (TSAd-SH2) under the control of the $p56^{lck}$ proximal promoter. In T cells from TSAd-SH2 TG mice, T cell receptor (TCR)-mediated early signaling events, such as $Ca^{2+}$ flux and ERK activation, were normal; however, late activation events, such as IL-2 production and proliferation, were significantly reduced. Moreover, TCR-induced cell adhesion to extracellular matrix (ECM) proteins and migration through ECM proteins were defective in T cells from TSAd-SH2 TG mice. Furthermore, the contact hypersensitivity (CHS) reaction, an inflammatory response mainly mediated by T helper 1 (Th1) cells, was inhibited in TSAd-SH2 TG mice. Taken together, these results show that TSAd, particularly the SH2 domain of TSAd, is essential for the effector functions of T cells.
Keywords
adhesion; Lad; migration; SH2 domain; TSAd;
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