Journal Article

Galectin-3 negatively regulates TCR-mediated CD4 super(+) T-cell activation at the immunological synapse

Yang, Ri-Yao, Chen, Huan-Yuan, Chang, En-Yuh, Weng, I-Chun, Maverakis, Emanual, Liu, Fu-Tong, Fermin, Agnes, Dustin, Michael L, Vardhana, Santosh, Hsu, Daniel K, Lo, Kin Fong Robin

2009

Overview

We have investigated the function of endogenous galectin-3 in T cells. Galectin-3-deficient (gal3 super(-/- )) CD4 super(+) T cells secreted more IFN- gamma and IL-4 than gal3 super(+/+)CD4 super(+) T cells after T-cell receptor (TCR) engagement. Galectin-3 was recruited to the cytoplasmic side of the immunological synapse (IS) in activated T cells. In T cells stimulated on supported lipid bilayers, galectin-3 was primarily located at the peripheral supramolecular activation cluster (pSMAC). Gal3 super(+/+) T cells formed central SMAC on lipid bilayers less effectively and adhered to antigen-presenting cells less firmly than gal3 super(-/-) T cells, suggesting that galectin-3 destabilizes the IS. Galectin-3 expression was associated with lower levels of early signaling events and phosphotyrosine signals at the pSMAC. Additional data suggest that galectin-3 potentiates down-regulation of TCR in T cells. By yeast two-hybrid screening, we identified as a galectin-3-binding partner, Alix, which is known to be involved in protein transport and regulation of cell surface expression of certain receptors. Co- immunoprecipitation confirmed galectin-3-Alix association and immunofluorescence analysis demonstrated the translocation of Alix to the IS in activated T cells. We conclude that galectin-3 is an inhibitory regulator of T-cell activation and functions intracellularly by promoting TCR down-regulation, possibly through modulating Alix's function at the IS.