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Summary: Engagement of inhibitory natural killer (NK) cell receptors for MHC class I molecules (NKR) can impair NK-cell activation programs. Inhibitory NKR thus confer to NK cells the capacity to discriminate between MHC class I+ and MHC class I target cells, and are therefore involved in the control of NK-cell tolerance to self, as well as in the elimination of MHC class I distressed cells by NK cells. In human and mouse, a subset of αβ T cells also express inhibitory NKR at their surface, but the biological function of inhibitory NKR on T cells remains to be precisely elucidated. We refer to these cells as T memory type 1 (Tm1) cells, and review here the phenotypic and functional features of this subset of memory-phenotype CD8+αβ T cells. In vitro studies suggest that inhibitory NKR are involved in the peripheral control of T-cell self-tolerance. In vitro and in vivo analysis have revealed a novel biological function for inhibitory NKR when expressed on T cells. Indeed, engagement of inhibitory NKR on T cells provides them with survival signals against activation-induced cell death. Thus, sensing of self-MHC class I molecules by inhibitory NKR displayed on αβ T cells leads to the in vivo accumulation of Tm1 cells.

The authors thank C. Arpin, J. Marvel (INSERM 503, CERVI, Lyon), C. Melief, R. Toes (Leiden University Medical Center, The Netherlands), D. Raulet (Berkeley, USA) and N. Glaichenhaus (IPMC, Nice) for helpful discussions and help, as well as F. Romagné (Immunotech) for the generous gift of MHC class I tetramers. This work was 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 (E. V., Equipe labellisée La Ligue; S. U.), from Association pour la Recherche contre le Cancer (E.V.), and from SIDACTION (S.U.).