Surface expression of the IFN-gamma R2 chain is regulated by intracellular trafficking in human T lymphocytes

The surface and cytoplasmic expressions of the transducing chain (IFN-gamma R2) of the heterodimeric IFN-gamma receptor on human T lymphocytes have been investigated. We show that its surface expression is low, whereas high cytoplasmic levels are found in both resting and PHA-activated T lymphocytes. This low expression does not prevent activated T cells from responding to IFN-gamma, because it induces IFN-regulatory factor 1 expression. Low surface IFN-gamma R2 expression appears to be due to recycling between cytoplasmic stores and the cell surface, which does not depend on signals mediated by endogenous IFN-gamma, because IFN-gamma R2 surface expression is low, and its internalization is equally observed in patients with inherited IFN-gamma R1 gene deficiency and in healthy donors. Moreover, IFN-gamma R2 internalization in T lymphoblasts from healthy donors was not affected by the presence of anti-IFN-gamma-neutralizing or anti-IFN-gamma R1-blocking mAb. In conclusion, these data illustrate a new mechanism whereby human T cells limit the surface expression of IFN-gamma R2 in a ligand-independent manner.