BETA-GALACTOSIDE-BINDING PROTEIN (BETA-GBP) ALTERS THE CELL-CYCLE, UP-REGULATES EXPRESSION OF THE ALPHA-CHAINS AND BETA-CHAINS OF THE IFN-GAMMA RECEPTOR, AND TRIGGERS IFN-GAMMA-MEDIATED APOPTOSIS OF ACTIVATED HUMAN T-LYMPHOCYTES

In this paper, the effects of beta-galactoside binding protein (beta G BP), the LGALS1 gene product, on the cell cycle progression and expans ion of activated human T lymphocytes were studied. beta GBP drasticall y inhibits the IL-2 induced proliferation of PHA-activated T lymphocyt es as well as the IL-2 independent proliferation of malignant T lympho cytes by arresting them in the S and G(2)/M phases of the cell cycle. In addition, beta GBP up-regulates the expression of both the alpha- a nd the beta-chains of the IFN-gamma R on activated T lymphocyte membra ne. None of these effects depend on sugar binding: saturating amounts of lactose do not affect the cell cycle block nor IFN-gamma R up-modul ation. The increased expression of both chains renders beta GBP-treate d T lymphoblasts sensitive to IFN-gamma-induced apoptosis, Taken as a whole, these findings suggest that beta GBP plays an important immunor egulatory role by switching off T lymphocyte effector functions, They also provide the first evidence of up-modulation of IFN-gamma R expres sion on T lymphocytes by a negative cell growth regulator.