A. Allione et al., Nitric oxide suppresses human T lymphocyte proliferation through IFN-gamma-dependent and IFN-gamma-independent induction of apoptosis, J IMMUNOL, 163(8), 1999, pp. 4182-4191
Human normal and malignant T cells cease to proliferate, down-modulate Bcl-
2 expression, and undergo apoptosis when cultured in the presence of NO-don
or compounds (sodium nitroprusside and NOC12) for 48 h, At 72 h, cells that
evade apoptosis start to proliferate again, overexpress both chains of the
IFN-gamma R, and thus become susceptible to apoptosis in the presence of I
FN-gamma. By contrast, in the presence of IFN-gamma, no apoptosis, but an i
ncrease of proliferation was displayed by control cultures of T cells not e
xposed to NO and not overexpressing IFN-gamma R chains. The NO-induced cell
surface overexpression of IFN-gamma R chains did not affect the transducti
on of IFN-gamma-mediated signals, as shown by the expression of the transcr
iption factor IFN regulatory factor I (IRF-1). However, transduction of the
se signals was quantitatively modified, because IFN-gamma induces enhanced
levels of caspase-1 effector death in NO-treated cells, These findings iden
tify NO as one of the environmental factors that critically govern the resp
onse of T cells to IFN-gamma By inducing the overexpression of IFN-gamma R
chains, NO decides whether IFN-gamma promotes cell proliferation or the ind
uction of apoptosis.