Involvement of inhibitory NKRs in the survival of a subset of memory-phenotype CD8+ T cells
Sophie Ugolini1, 7, Christophe Arpin2, Nicolas Anfossi1, Thierry Walzer2, Anna Cambiaggi3, Reinhold Förster4, Martin Lipp4, René E. M. Toes5, Cornelius J. Melief5, Jacqueline Marvel2
& Eric Vivier1, 6
1
Centre d'Immunologie INSERM/CNRS de Marseille-Luminy, Case 906, 13288 Marseille CEDEX 09, France.
2
INSERM U503, CERVI Lyon, France.
3
Sir William Dunn School of Pathology, University of Oxford, UK.
4
Max-Delbrueck-Center for Molecular Medicine, Berlin-Buch, Germany.
5
Department of Immunohematology and Bloodbank, Leiden University Medical Center, The Netherlands.
6
Institut Universitaire de France.
7
Present address: Institut de Pharmacologie Moléculaire et Cellulaire, 660 Route des Lucioles, 06560 Valbonne, France.
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 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.
NOTE: Incorrect reference numbering appeared in both the original print and web versions of this article. The instances of these errors are marked by asterisks (*) in the online version. The errors are: (i) Ref. 28 was printed incorrectly and should be Ref. 31; (ii) Ref. 29 was printed incorrectly and should be Ref. 32; (iii) References 28−32 should read as follows: 28. Zajac, A. J. et al. Impaired Anti-viral T cell responses due to expression of the LY49A inhibitory receptor. J. Immunol. 163, 5526-5534 (1999).
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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.
