Beta-galactoside-binding protein (beta GBP) alters the cell cycle, up-regulates expression of the alpha- 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 GBP), the LGALS1 gene product, on the cell cycle progression and expansion of activated human T lymphocytes were studied. Beta GBP 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, beta GBP up-regulates the expression of both the alpha- and the beta-chains of the IFN-gamma R 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-gamma R up-modulation. The increased expression of both chains renders beta GBP-treated T lymphoblasts sensitive to IFN-y-induced apoptosis. Taken as a whole, these findings suggest that beta GBP plays an important immunoregulatory role by switching off T lymphocyte effector functions. They also provide the first evidence of up-modulation of IFN-gamma R expression on T lymphocytes by a negative cell growth regulator.
Allione
A
A
Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy.
Wells
V
V
Forni
G
G
Mallucci
L
L
Novelli
F
F
D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D002453:Cell Cycle / Q000187:drug effects / Q000276:immunology*; D005697:Galactosides / Q000378:metabolism; D037483:Galectin 1; D006388:Hemagglutinins / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology*; D007376:Interleukin-2 / Q000502:physiology; D037102:Lectins / Q000378:metabolism / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D017471:Receptors, Interferon / Q000096:biosynthesis* / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism; D014316:Tritium; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology*; D000096743:Interferon gamma Receptor
D005697:Galactosides; D037483:Galectin 1; D006388:Hemagglutinins; D007371:Interferon-gamma; D007376:Interleukin-2; D037102:Lectins; D017471:Receptors, Interferon; D013936:Thymidine; D014316:Tritium; D000096743:Interferon gamma Receptor