β-Galactoside-Binding Protein (βGBP) Alters the Cell Cycle, Up-Regulates Expression of the α- and β-Chains of the IFN-γ Receptor, and Triggers IFN-γ-Mediated Apoptosis of Activated Human T Lymphocytes

Abstract

AbstractIn this paper, the effects of β-galactoside binding protein (βGBP), the LGALS1 gene product, on the cell cycle progression and expansion of activated human T lymphocytes were studied. βGBP drastically inhibits the IL-2 induced proliferation of PHA-activated T lymphocytes as well as the IL-2 independent proliferation of malignant T lymphocytes by arresting them in the S and G2/M phases of the cell cycle. In addition, βGBP up-regulates the expression of both the α- and the β-chains of the IFN-γR on activated T lymphocyte membrane. None of these effects depend on sugar binding: saturating amounts of lactose do not affect the cell cycle block nor IFN-γR up-modulation. The increased expression of both chains renders βGBP-treated T lymphoblasts sensitive to IFN-γ-induced apoptosis. Taken as a whole, these findings suggest that βGBP plays an important immunoregulatory role by switching off T lymphocyte effector functions. They also provide the first evidence of up-modulation of IFN-γR expression on T lymphocytes by a negative cell growth regulator.