The effector functions of mature T lymphocytes are impaired in transgenic mice expressing the SH2 domain of TSAd/Lad |
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| Authors: | Youngbong Choi Eunkyung Park Eunseon Ahn Inyoung Park Yungdae Yun |
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| Institution: | (1) Department of Anatomy, Institute of Basic Medical Sciences, University of Oslo, P.O. Box 1105, Blindern, 0317 Oslo, Norway;(2) NIH-Karolinska Institutet Graduate Partnership Program, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, NIH, 12441 Parklawn Drive, Rockville, MD 20852, USA;(3) Institute of Immunology, Rikshospitalet University Hospital, 0027 Oslo, Norway; |
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| 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 Ca2+ 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. |
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