Novelli F, Bernabei P, Ozmen L, Rigamonti L, Allione A, Pestka S, Garotta G, Forni G
Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy.
J Immunol. 1996 Sep 1;157(5):1935-43.
To find out how physiologically secreted IFN-gamma controls either the proliferation or the apoptosis of human T lymphocytes, the kinetics of expression of the alpha- and beta-chains of its receptor (IFN-gamma R) were sequentially followed on T lymphocytes first activated with PHA and then cultured in the presence of IL-2, and related to the kinetics of expression of Fas, Bcl-2, and IL-2R p55 chain. Both IFN-gamma R chains were poorly expressed on the membrane of resting T lymphocytes. Following their stimulation with PHA, IFN-gamma R alpha but not IFN gamma R beta-chain up-modulated before T lymphocyte entry into the S phase, and then IFN-gamma R alpha down-modulated when they passed through the S and G2/M. The ensuing proliferative response was inhibited by an anti-IFN-gamma R alpha mAb that impeded the binding of IFN-gamma. When PHA-activated T lymphoblasts were cultured for 16 days with IL-2, IFN-gamma R alpha expression increased, whereas that of the beta-chain remained barely detectable. Fas and Bcl-2 were both highly expressed. When these T lymphoblasts were restimulated by PHA, OKT3, or Staphylococcus enterotoxin beta-pokeweed mitogen, both chains up-modulated and most cells underwent apoptosis in a way apparently independent of Bcl-2, but not of Fas. This apoptosis, too, was prevented by the anti-IFN-gamma R alpha mAb. Physiologically secreted IFN-gamma is thus involved in the activation of resting T lymphocytes and in the apoptosis of reactivated lymphoblasts. However, high expression of IFN-gamma R beta took place when IFN-gamma induced apoptosis, but not when it induced proliferation. In conclusion, a correlation exists between differential expression of the IFN-gamma R beta-chain and the delivery by IFN-gamma of proliferative or apoptotic signals.
为了探究生理分泌的γ干扰素（IFN-γ）如何控制人T淋巴细胞的增殖或凋亡，我们首先用PHA激活T淋巴细胞，然后在白细胞介素-2（IL-2）存在的情况下进行培养，依次跟踪其受体（IFN-γR）α链和β链的表达动力学，并将其与Fas、Bcl-2和IL-2R p55链的表达动力学相关联。IFN-γR的两条链在静止T淋巴细胞的膜上表达都很低。在用PHA刺激后，IFN-γRα链而非β链在T淋巴细胞进入S期之前上调，然后在它们通过S期和G2/M期时下调。随后的增殖反应被一种抗IFN-γRα单克隆抗体抑制，该抗体阻碍了IFN-γ的结合。当PHA激活的T淋巴母细胞用IL-2培养16天时，IFN-γRα的表达增加，而β链的表达仍然几乎检测不到。Fas和Bcl-2都高度表达。当这些T淋巴母细胞被PHA、OKT3或葡萄球菌肠毒素β-美洲商陆丝裂原再次刺激时，两条链都上调，并且大多数细胞以一种显然独立于Bcl-2但不独立于Fas的方式发生凋亡。这种凋亡也被抗IFN-γRα单克隆抗体阻止。因此，生理分泌的IFN-γ参与静止T淋巴细胞的激活和再激活的淋巴母细胞的凋亡。然而，当IFN-γ诱导凋亡时，IFN-γRβ高度表达，但在诱导增殖时则不然。总之，IFN-γRβ链的差异表达与IFN-γ传递增殖或凋亡信号之间存在相关性。
