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* Microbiology, Immunology, and Molecular Genetics, and
Molecular Biology Institute, University of California, Los Angeles, CA 90066;
Biomedical Research Institute, Department of Medicine, Torrance, CA 90502; and
Institut Jacques Monod, Centre National de la Recherche Scientifique Unité Mixte de Recherche 75921, P6 and P7 Universities, Paris, France
T cell burst size is regulated by the duration of TCR engagement and balanced control of Ag-induced activation, expansion, and apoptosis. We found that galectin-1-deficient CD8 T cells undergo greater cell division in response to TCR stimulation, with fewer dividing cells undergoing apoptosis. TCR-induced ERK signaling was sustained in activated galectin-1-deficient CD8 T cells and antagonized by recombinant galectin-1, indicating galectin-1 modulates TCR feed-forward/feedback loops involved in signal discrimination and procession. Furthermore, recombinant galectin-1 antagonized binding of agonist tetramers to the TCR on activated OT-1 T cells. Finally, galectin-1 produced by activated Ag-specific CD8 T cells negatively regulated burst size and TCR avidity in vivo. Therefore, galectin-1, inducibly expressed by activated CD8 T cells, functions as an autocrine negative regulator of peripheral CD8 T cell TCR binding, signal transduction, and burst size. Together with recent findings demonstrating that gal-1 promotes binding of agonist tetramers to the TCR of OT-1 thymocytes, these studies identify galectin-1 as a tuner of TCR binding, signaling, and functional fate determination that can differentially specify outcome, depending on the developmental and activation stage of the T cell.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by Grant NIH R01A1056155 (to M.C.M.). S.D.L. was supported by the Microbial Pathogenesis Training Grant T32 AI07323-15, Clinical and Fundamental Training Grant AI07126-30, and Warsaw Fellowship. T.T. is a recipient of the Microbial Pathogenesis Training Grant 2-T32-AI-07323. F.P. received financial support from Association pour la Recherche sur le Cancer and Ligue Contre le Cancer. University of California Jonsson Comprehensive Cancer Center and Center for AIDS Research Flow Cytometry Core Facility were supported by National Institutes of Health Awards CA-16042 and AI-28697.
2 Address correspondence and reprint requests to Dr. M. Carrie Miceli, Department of Microbiology, Immunology, and Molecular Genetics, University of California, 277B Biomedical Sciences Research Building, 615 Charles East Young Drive S., Los Angeles, CA 90095-1570. E-mail address: cmiceli{at}ucla.edu
3 Abbreviations used in this paper: gal-1, galectin-1; AINR, activation-induced nonresponsiveness; LCMV, lymphocytic choriomeningitis virus; MFI, mean fluorescent intensity; pERK, phosphorylated ERK; SHP-1, Src homology region 2 domain-containing phosphatase 1; TNE, 50 mM Tris, 1% Nonidet P-40, 2 mM EDTA, pH 8.0.
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