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Departments of
*
Microbiology and Immunology and
Pathology and Laboratory Medicine, and
Molecular Biology Institute, University of California, Los Angeles, School of Medicine, Los Angeles, CA 90095
Galectin-1 is an endogenous lectin expressed by thymic and lymph node stromal cells at sites of Ag presentation and T cell death during normal development. It is known to have immunomodulatory activity in vivo and can induce apoptosis in thymocytes and activated T cells (1–3). Here we demonstrate that galectin-1 stimulation cooperates with TCR engagement to induce apoptosis, but antagonizes TCR-induced IL-2 production and proliferation in a murine T cell hybridoma and freshly isolated mouse thymocytes, respectively. Although CD4+CD8+ double positive cells are the primary thymic subpopulation susceptible to galectin-1 treatment alone, concomitant CD3 engagement and galectin-1 stimulation broaden susceptible thymocyte subpopulations to include a subset of each CD4-CD8-, CD4+CD8+, CD4-CD8+, and CD4+CD8- subpopulations. Furthermore, CD3 engagement cooperates with suboptimal galectin-1 stimulation to enhance cell death in the CD4+CD8+ subpopulation. Galectin-1 stimulation is shown to synergize with TCR engagement to dramatically and specifically enhance extracellular signal-regulated kinase-2 (ERK-2) activation, though it does not uniformly enhance TCR-induced tyrosine phosphorylation. Unlike TCR-induced IL-2 production, TCR/galectin-1-induced apoptosis is not modulated by the expression of kinase inactive or constitutively activated Lck. These data support a role for galectin-1 as a potent modulator of TCR signals and functions and indicate that individual TCR-induced signals can be independently modulated to specifically affect distinct TCR functions.
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N. Maeda, N. Kawada, S. Seki, T. Arakawa, K. Ikeda, H. Iwao, H. Okuyama, J. Hirabayashi, K.-i. Kasai, and K. Yoshizato Stimulation of Proliferation of Rat Hepatic Stellate Cells by Galectin-1 and Galectin-3 through Different Intracellular Signaling Pathways J. Biol. Chem., May 23, 2003; 278(21): 18938 - 18944. [Abstract] [Full Text] [PDF]
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 M. J. Abedin, Y. Kashio, M. Seki, K. Nakamura, and M. Hirashima Potential roles of galectins in myeloid differentiation into three different lineages J. Leukoc. Biol., May 1, 2003; 73(5): 650 - 656. [Abstract] [Full Text] [PDF]
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M. Amano, M. Galvan, J. He, and L. G. Baum The ST6Gal I Sialyltransferase Selectively Modifies N-Glycans on CD45 to Negatively Regulate Galectin-1-induced CD45 Clustering, Phosphatase Modulation, and T Cell Death J. Biol. Chem., February 21, 2003; 278(9): 7469 - 7475. [Abstract] [Full Text] [PDF]
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 L. Dettin, N. Rubinstein, A. Aoki, G. A. Rabinovich, and C. A. Maldonado Regulated Expression and Ultrastructural Localization of Galectin-1, a Proapoptotic {beta}-Galactoside-Binding Lectin, During Spermatogenesis in Rat Testis Biol Reprod, January 1, 2003; 68(1): 51 - 59. [Abstract] [Full Text] [PDF]
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J. D. Hernandez and L. G. Baum Ah, sweet mystery of death! Galectins and control of cell fate Glycobiology, October 1, 2002; 12(10): 127R - 136R. [Abstract] [Full Text] [PDF]
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G. A. Rabinovich, N. Rubinstein, and L. Fainboim Unlocking the secrets of galectins: a challenge at the frontier of glyco-immunology J. Leukoc. Biol., May 1, 2002; 71(5): 741 - 752. [Abstract] [Full Text] [PDF]
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J. L. Dunphy, G. J. Barcham, R. J. Bischof, A. R. Young, A. Nash, and E. N. T. Meeusen Isolation and Characterization of a Novel Eosinophil-specific Galectin Released into the Lungs in Response to Allergen Challenge J. Biol. Chem., April 19, 2002; 277(17): 14916 - 14924. [Abstract] [Full Text] [PDF]
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 K. Goldring, G. E. Jones, R. Thiagarajah, and D. J. Watt The effect of galectin-1 on the differentiation of fibroblasts and myoblasts in vitro J. Cell Sci., January 15, 2002; 115(2): 355 - 366. [Abstract] [Full Text] [PDF]
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J. T. Nguyen, D. P. Evans, M. Galvan, K. E. Pace, D. Leitenberg, T. N. Bui, and L. G. Baum CD45 Modulates Galectin-1-Induced T Cell Death: Regulation by Expression of Core 2 O-Glycans J. Immunol., November 15, 2001; 167(10): 5697 - 5707. [Abstract] [Full Text] [PDF]
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H.-G. Joo, P. S Goedegebuure, N. Sadanaga, M. Nagoshi, W. von Bernstorff, and T. J. Eberlein Expression and function of galectin-3, a {beta}-galactoside-binding protein in activated T lymphocytes J. Leukoc. Biol., April 1, 2001; 69(4): 555 - 564. [Abstract] [Full Text]
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 M. A. Berger, M. Carleton, M. Rhodes, J. M. Sauder, S. Trop, R. L. Dunbrack, P. Hugo, and D. L. Wiest Identification of a novel pre-TCR isoform in which the accessibility of the TCR{beta} subunit is determined by occupancy of the `missing' V domain of pre-T{alpha} Int. Immunol., November 1, 2000; 12(11): 1579 - 1591. [Abstract] [Full Text] [PDF]
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C. D. Chung, V. P. Patel, M. Moran, L. A. Lewis, and M. C. Miceli Galectin-1 Induces Partial TCR {zeta}-Chain Phosphorylation and Antagonizes Processive TCR Signal Transduction J. Immunol., October 1, 2000; 165(7): 3722 - 3729. [Abstract] [Full Text] [PDF]
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K. E. Pace, H. P. Hahn, M. Pang, J. T. Nguyen, and L. G. Baum Cutting Edge: CD7 Delivers a Pro-Apoptotic Signal During Galectin-1-Induced T Cell Death J. Immunol., September 1, 2000; 165(5): 2331 - 2334. [Abstract] [Full Text] [PDF]
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M. Fouillit, R. Joubert-Caron, F. Poirier, P. Bourin, E. Monostori, M. Levi-Strauss, M. Raphael, D. Bladier, and M. Caron Regulation of CD45-induced signaling by galectin-1 in Burkitt lymphoma B cells Glycobiology, April 1, 2000; 10(4): 413 - 419. [Abstract] [Full Text] [PDF]
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K. E. Pace, C. Lee, P. L. Stewart, and L. G. Baum Restricted Receptor Segregation into Membrane Microdomains Occurs on Human T Cells During Apoptosis Induced by Galectin-1 J. Immunol., October 1, 1999; 163(7): 3801 - 3811. [Abstract] [Full Text] [PDF]
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 G. A. Rabinovich, G. Daly, H. Dreja, H. Tailor, C. M. Riera, J. Hirabayashi, and Y. Chernajovsky Recombinant Galectin-1 and Its Genetic Delivery Suppress Collagen-Induced Arthritis via T Cell Apoptosis J. Exp. Med., August 2, 1999; 190(3): 385 - 398. [Abstract] [Full Text] [PDF]
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O. Dienz, S. P. Hehner, W. Droge, and M. L. Schmitz Synergistic Activation of NF-kappa B by Functional Cooperation between Vav and PKCtheta in T Lymphocytes J. Biol. Chem., August 4, 2000; 275(32): 24547 - 24551. [Abstract] [Full Text] [PDF]
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M. Galvan, S. Tsuboi, M. Fukuda, and L. G. Baum Expression of a Specific Glycosyltransferase Enzyme Regulates T Cell Death Mediated by Galectin-1 J. Biol. Chem., May 26, 2000; 275(22): 16730 - 16737. [Abstract] [Full Text] [PDF]
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