Involvement of inhibitory NKRs in the survival of a subset of memory-phenotype CD8+ T cells.
Inhibitory natural killer receptors (NKRs) such as killer cell immunoglobulin-like receptors (KIRs) in humans and Ly49 molecules in mice are expressed on NK cells and recognize multiple major histocompatibility (MHC) class I proteins. In humans and mice, a subset of CD8+ T cells also expresses NKRs and harbors a memory phenotype. Using mice that are transgenic for KIR2DL3 and its cognate HLA-Cw3 ligand, we show that engagement of inhibitory NKRs selectively drives the in vivo accumulation of a subset of memory-phenotype CD8+ T cells that express the beta chain of the interleukin 2 receptor. In vitro, recognition of MHC class I molecules by inhibitory NKRs on T cells down-regulated activation-induced cell death. These results unveil an MHC class I-dependent pathway that promotes the survival of a subset of memory-phenotype CD8+ T cells and also reveal an unexpected biological function for inhibitory NKRs on T cells.
Ugolini
S
S
Centre d'Immunologie INSERM/CNRS de Marseille-Luminy, Case 906, 13288 Marseille, France.
Arpin
C
C
Anfossi
N
N
Walzer
T
T
Cambiaggi
A
A
Förster
R
R
Lipp
M
M
Toes
R E
RE
Melief
C J
CJ
Marvel
J
J
Vivier
E
E
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016923:Cell Death; D015236:HLA-C Antigens / Q000235:genetics / Q000276:immunology; D007156:Immunologic Memory; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology*; D054340:Receptors, KIR; D054344:Receptors, KIR2DL3; D013154:Spleen / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014611:Vaccination
D015236:HLA-C Antigens; C038653:HLA-C*03 antigen; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D054344:Receptors, KIR2DL3