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R2 Chain Is Regulated by Intracellular Trafficking in Human T Lymphocytes1
*
Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy;
Department of Experimental Medicine and Pathology, "La Sapienza" University, Rome, Italy; and
Hôpital Necker-Enfants Malades, Institut National de la Santé et de la Recherche Médicale, Unité 429, Paris, France
The surface and cytoplasmic expressions of the transducing chain
(IFN-
R2) of the heterodimeric IFN- 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-, because it induces
IFN-regulatory factor 1 expression. Low surface IFN-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-, because IFN-R2 surface expression is low, and its
internalization is equally observed in patients with inherited
IFN-R1 gene deficiency and in healthy donors. Moreover, IFN-R2
internalization in T lymphoblasts from healthy donors was not affected
by the presence of anti-IFN--neutralizing or
anti-IFN-R1-blocking mAb. In conclusion, these data illustrate a
new mechanism whereby human T cells limit the surface expression of
IFN-R2 in a ligand-independent manner.
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