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- and ß-Chains of the IFN-
Receptor, and Triggers IFN--Mediated Apoptosis of Activated Human T Lymphocytes1
,
*
Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy;
Division of Life Sciences, Cell Growth Regulation Laboratory, King’s College, London, United Kingdom; and
Department of Medicine, G. D’Annunzio University, Chieti, Italy
In this paper, the effects of ß-galactoside binding protein
(ßGBP), the LGALS1 gene product, on the cell cycle
progression and expansion of activated human T lymphocytes were
studied. ßGBP 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, ßGBP
up-regulates the expression of both the 
- and the ß-chains of the
IFN-
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-R up-modulation. The increased
expression of both chains renders ßGBP-treated T lymphoblasts
sensitive to IFN--induced apoptosis. Taken as a whole, these
findings suggest that ßGBP plays an important immunoregulatory role
by switching off T lymphocyte effector functions. They also provide the
first evidence of up-modulation of IFN-R expression on T lymphocytes
by a negative cell growth regulator.
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