Modulation of interferon‐γ receptor during human T lymphocyte alloactivation

Previous work has shown that neutralization of physiologically secreted interferon(IFN)‐γ or blockade of its receptor during T lymphocyte activation inhibits both proliferation and cytotoxic T lymphocyte generation, suggesting that IFN‐γ plays a crucial role in T lymphocyte induction and differentiation. In this study, the kinetics of the surface expression of the 90‐kDa IFN‐γ receptor (IFN‐γR) was followed during human mixed lymphocyte reaction (MLR) to alloantigens. IFN‐γR mRNA is constitutively expressed on resting peripheral blood lymphocytes emerging from nylon wood column (NW‐PBL) and its expression increases two‐ to threefold on alloactivated NW‐PBL. IFN‐γR protein is poorly expressed on the membrane of resting CD3 cells, but up‐modulates after 3‐day MLR and sharply down‐modulates at day 6. Both the p55 and the p75 chains of interleukin‐2 receptor (IL‐2R) were shown to up‐modulate in parallel with IFN‐γR, whereas they were still highly expressed at day 6. After alloactivation, IFN‐γ and IL‐2 secretion starts at 24 h, peaks at day 3 and decreases just when IFN‐γR and IL‐2R begin to up‐modulate. Proliferation peaks at day 6. Lastly, stimulation with distinct cell populations showed that the intensity of lymphocyte proliferation, IFN‐γR membrane up‐modulation, and IFN‐γ and IL‐2 secretion are regulated in a parallel manner, thus suggesting that they are interrelated. Taken as whole these results demonstrate that increased expression of IFN‐γR on T lymphocytes can be a critical event during their activation, and strongly support the hypothesis that IFN‐γ/IFN‐γR interaction provides a signal for its progression. Copyright © 1993 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim