Coordinated expression of Ig-like inhibitory MHC class I receptors and acquisition of cytotoxic function in human CD8+ T cells.
MHC class I-specific inhibitory receptors are expressed by a subset of memory-phenotype CD8(+) T cells. Similar to NK cells, MHC class I-specific inhibitory receptors might subserve on T cells an important negative control that participates to the prevention of autologous damage. We analyzed here human CD8(+) T cells that express the Ig-like MHC class I-specific inhibitory receptors: killer cell Ig-like receptor (KIR) and CD85j. The cell surface expression of Ig-like inhibitory MHC class I receptors was found to correlate with an advanced stage of CD8(+) T cell maturation as evidenced by the reduced proliferative potential of KIR(+) and CD85j(+) T cells associated with their high intracytoplasmic perforin content. This concomitant regulation might represent a safety mechanism to control potentially harmful cytolytic CD8(+) T cells, by raising their activation threshold. Yet, KIR(+) and CD85j(+) T cells present distinct features. KIR(+)CD8(+) T cells are poor IFN-gamma producers upon TCR engagement. In addition, KIR are barely detectable at the surface of virus-specific T cells during the course of CMV or HIV-1 infection. By contrast, CD85j(+)CD8(+) T cells produce IFN-gamma upon TCR triggering, and represent a large fraction of virus-specific T cells. Thus, the cell surface expression of Ig-like inhibitory MHC class I receptors is associated with T cell engagement into various stages of the cytolytic differentiation pathway, and the cell surface expression of CD85j or KIR witnesses to the history of qualitatively and/or quantitatively distinct T cell activation events.
Anfossi
Nicolas
N
Centre d'Immunologie de Marseille-Luminy, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de la Méditerranée, Marseille, France.
Doisne
Jean-Marc
JM
Peyrat
Marie-Alix
MA
Ugolini
Sophie
S
Bonnaud
Olivia
O
Bossy
David
D
Pitard
Vincent
V
Merville
Pierre
P
Moreau
Jean-François
JF
Delfraissy
Jean-François
JF
Dechanet-Merville
Julie
J
Bonneville
Marc
M
Venet
Alain
A
Vivier
Eric
E
D015703:Antigens, CD / Q000096:biosynthesis* / Q000097:blood; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D049109:Cell Proliferation; D002999:Clone Cells; D003586:Cytomegalovirus Infections / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic; D015497:HIV-1 / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D016030:Kidney Transplantation / Q000009:adverse effects / Q000276:immunology; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis; D011971:Receptors, Immunologic / Q000096:biosynthesis* / Q000097:blood; D054340:Receptors, KIR
D015703:Antigens, CD; D015395:Histocompatibility Antigens Class I; C105299:LILRB1 protein, human; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; D054340:Receptors, KIR