Expansion and function of CD8+ T cells expressing Ly49 inhibitory receptors specific for MHC class I molecules.
MHC class I-specific Ly49 inhibitory receptors regulate NK cell activation, thereby preventing autologous damage to normal cells. Ly49 receptors are also expressed on a subset of CD8+ T cells whose origin and function remain unknown. We report here that, despite their phenotypic and cytolytic similarities, Ly49+CD8+ T cells and conventional Ly49-CD44high memory-phenotype CD8+ T cells present strikingly distinct features. First, under steady state conditions Ly49+CD8+ T cells are poor cytokine producers (TNF-alpha and IFN-gamma) upon TCR triggering. Second, Ly49+CD8+ T cells are not induced upon various settings of Ag immunization or microbial challenge. However, Ly49 can be induced on a fraction of self-specific CD8+ T cells if CD4+ T cells are present. Finally, the size of the Ly49+CD8+ T cell subset is selectively reduced in the absence of STAT1. These results indicate that Ly49 expression is associated with a differentiation program of cytolytic CD8+ T cells triggered upon chronic antigenic exposure. They further suggest that the size of the Ly49+CD8+ T cell subset marks a history of CD8+ T cell activation that might preferentially result from endogenous inducers of inflammation rather than from microbial infections.
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, Campus de Luminy, Marseille, France.
Robbins
Scott H
SH
Ugolini
Sophie
S
Georgel
Philippe
P
Hoebe
Kasper
K
Bouneaud
Cécile
C
Ronet
Catherine
C
Kaser
Arthur
A
DiCioccio
Catherine B
CB
Tomasello
Elena
E
Blumberg
Richard S
RS
Beutler
Bruce
B
Reiner
Steven L
SL
Alexopoulou
Lena
L
Lantz
Olivier
O
Raulet
David H
DH
Brossay
Laurent
L
Vivier
Eric
E
D000818:Animals; D000950:Antigens, Ly / Q000096:biosynthesis* / Q000502:physiology; D024201:Bystander Effect / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000096:biosynthesis* / Q000502:physiology; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D055630:Receptors, NK Cell Lectin-Like; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism
D000950:Antigens, Ly; D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; D037181:Lectins, C-Type; D011948:Receptors, Antigen, T-Cell; D055630:Receptors, NK Cell Lectin-Like