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 β 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). 29. Pauza, M. et al. Transgenic expression of Ly-49A in thymocytes alters repertoire selection. J. Immunol. 164, 884-892 (2000). 30. Fahlen, L. et al. Ly49A expression on T cells alters T cell selection. Int. Immunol. 12, 215-222 (2000). 31. Marti, F. et al. LCK-phosphorylated human killer cell-inhibitory receptors recruit and activate phosphatidylinositol 3-kinase. Proc. Natl Acad. Sci. USA. 95, 11810-11815 (1998). 32. Bieganowska, K. et al. Direct analysis of viral-specific CD8+ T cells with soluble HLA-A2/Tax11-19 tetramer complexes in patients with human T cell lymphotropic virus-associated myelopathy. J. Immunol. 162, 1765-1771 (1999). We apologize for any confusion this may have caused. The most updated version of the article is available in PDF format.
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We thank F. Vély, V. Pascal (CIML) and M. Tomkowiak (U503) for helpful comments and S. Guerder, P. Golstein, B. Malissen, P. Naquet (CIML), D. Raulet (Berkeley), N. Glaichenhaus (IPMC, Valbonne, France) and M. Bonneville (INSERM U463, Nantes, France) for stimulating discussions. We also thank P. Hoest (Laboratoire Commun de Microbiologie NSB3, Faculté de Médecine de la Timone, Marseille, France). Supported by institutional grants from INSERM, CNRS, Ministère de l'Enseignement Supérieur et de la Recherche and specific grants from Ligue Nationale contre le Cancer (to E. V., Equipe Labélisée Ligue), from Association pour la Recherche contre le Cancer (to E. V. and J. M.), from SIDACTION (to S. U.) and from the Training and Mobility of Researcher Programme (to A. C.).
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