The effector functions of mature T lymphocytes are impaired in transgenic mice expressing the SH2 domain of TSAd/Lad.
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.
Choi
Youngbong
Y
Department of Life Science, Ewha Womans University, Seoul, Korea.
Park
Eunkyung
E
Ahn
Eunseon
E
Park
Inyoung
I
Yun
Yungdae
Y
D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis / Q000502:physiology*; D000818:Animals; D002448:Cell Adhesion / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D003877:Dermatitis, Contact / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000276:immunology*; D018909:src Homology Domains / Q000276:immunology
D048868:Adaptor Proteins, Signal Transducing; C402726:Sh2d2a protein, mouse; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)