Galectin-1 specifically modulates TCR signals to enhance TCR apoptosis but inhibit IL-2 production and proliferation

• Published in: The Journal of immunology (1950) Vol. 162; no. 2; pp. 799 - 806
• Main Authors: Vespa, G N, Lewis, L A, Kozak, K R, Moran, M, Nguyen, J T, Baum, L G, Miceli, M C
• Format: Journal Article
• Language: English
• Published: United States 15.01.1999
• Subjects: Adjuvants, Immunologic - pharmacology; Animals; Antibodies, Monoclonal - pharmacology; Apoptosis - drug effects; Apoptosis - genetics; Apoptosis - immunology; Arginine - genetics; Calcium-Calmodulin-Dependent Protein Kinases - metabolism; CD3 Complex - metabolism; CD4 Antigens - metabolism; CD8 Antigens - metabolism; Cell Separation; Drug Synergism; Enzyme Activation - genetics; Female; Galectin 1; Hemagglutinins - pharmacology; Humans; Hybridomas - enzymology; Hybridomas - immunology; Hybridomas - metabolism; Interleukin-2 - antagonists & inhibitors; Interleukin-2 - biosynthesis; Lymphocyte Activation - drug effects; Lymphocyte Activation - immunology; Lymphocyte Specific Protein Tyrosine Kinase p56(lck) - genetics; Lymphocyte Specific Protein Tyrosine Kinase p56(lck) - metabolism; Mice; Mice, Inbred C57BL; Mutagenesis, Site-Directed; Phenylalanine - genetics; Receptors, Antigen, T-Cell - immunology; Receptors, Antigen, T-Cell - metabolism; Receptors, Antigen, T-Cell - physiology; Signal Transduction - drug effects; Signal Transduction - immunology; T-Lymphocyte Subsets - enzymology; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; Thymus Gland - cytology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.162.2.799

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.