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.
Rigamonti
L
L
Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy.
Ariotti
S
S
Losana
G
G
Gradini
R
R
Russo
M A
MA
Jouanguy
E
E
Casanova
J L
JL
Forni
G
G
Novelli
F
F
D000069594:Abatacept; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000096:biosynthesis; D001692:Biological Transport / Q000276:immunology; D060908:CTLA-4 Antigen; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D002966:Clathrin / Q000502:physiology; D003593:Cytoplasm / Q000276:immunology / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D004705:Endocytosis / Q000276:immunology; D006801:Humans; D018796:Immunoconjugates; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000276:immunology; D050856:Interferon Regulatory Factor-1; D007371:Interferon-gamma / Q000378:metabolism* / Q000502:physiology; D007399:Interphase / Q000276:immunology; D007424:Intracellular Fluid / Q000276:immunology* / Q000378:metabolism*; D008213:Lymphocyte Activation; D010750:Phosphoproteins / Q000096:biosynthesis; D017471:Receptors, Interferon / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D000096743:Interferon gamma Receptor
D000069594:Abatacept; D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; D002966:Clathrin; D004268:DNA-Binding Proteins; D018796:Immunoconjugates; D050856:Interferon Regulatory Factor-1; D007371:Interferon-gamma; D010750:Phosphoproteins; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor; C556706:CTLA4 protein, human; C494257:IRF1 protein, human