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Mol. Cells 2009; 28(3): 183-188

Published online September 4, 2009

https://doi.org/10.1007/s10059-009-0121-0

© The Korean Society for Molecular and Cellular Biology

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

Youngbong Choi, Eunkyung Park, Eunseon Ahn, Inyoung Park, and Yungdae Yun

Received: April 21, 2009; Revised: July 20, 2009; Accepted: July 27, 2009

Abstract

TSAd/Lad is a T cell adaptor molecule involved in p56lck-mediated T cell activation. To investigate the functions of TSAd in T cells, we generated transgenic (TG) mice ex-pressing the SH2 domain of TSAd (TSAd-SH2) under the control of the p56lck 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.

Keywords adhesion, Lad, migration, SH2 domain, TSAd

Article

Research Article

Mol. Cells 2009; 28(3): 183-188

Published online September 30, 2009 https://doi.org/10.1007/s10059-009-0121-0

Copyright © The Korean Society for Molecular and Cellular Biology.

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

Youngbong Choi, Eunkyung Park, Eunseon Ahn, Inyoung Park, and Yungdae Yun

Received: April 21, 2009; Revised: July 20, 2009; Accepted: July 27, 2009

Abstract

TSAd/Lad is a T cell adaptor molecule involved in p56lck-mediated T cell activation. To investigate the functions of TSAd in T cells, we generated transgenic (TG) mice ex-pressing the SH2 domain of TSAd (TSAd-SH2) under the control of the p56lck 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.

Keywords: adhesion, Lad, migration, SH2 domain, TSAd

Mol. Cells
Sep 30, 2023 Vol.46 No.9, pp. 527~572
COVER PICTURE
Chronic obstructive pulmonary disease (COPD) is marked by airspace enlargement (emphysema) and small airway fibrosis, leading to airflow obstruction and eventual respiratory failure. Shown is a microphotograph of hematoxylin and eosin (H&E)-stained histological sections of the enlarged alveoli as an indicator of emphysema. Piao et al. (pp. 558-572) demonstrate that recombinant human hyaluronan and proteoglycan link protein 1 (rhHAPLN1) significantly reduces the extended airspaces of the emphysematous alveoli by increasing the levels of TGF-β receptor I and SIRT1/6, as a previously unrecognized mechanism in human alveolar epithelial cells, and consequently mitigates COPD.

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