Eric Vivier

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 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.

Activation of Human Endothelial Cells via S-Endo-1 Antigen (CD146) Stimulates the Tyrosine Phosphorylation of Focal Adhesion Kinase p125FAK

S-Endo-1 antigen (CD146), a transmembrane receptor also known as MUC18/MCAM, is a member of the immunoglobulin superfamily and belongs to a group of cell adhesion molecules. CD146 is highly expressed on the whole vascular tree. We demonstrate here that engagement of CD146 on human endothelial cells isolated from cord blood results in tyrosine phosphorylation of a large panel of cellular proteins, although no tyrosine phosphorylation of CD146 was detected. In particular, CD146 cross-linking induces the tyrosine phosphorylation of the protein tyrosine kinase p125FAK as well as p125FAK association with paxillin, both events being inhibited by cytochalasin D. No direct association of CD146 with p125FAK was observed. Consistent with these data, CD146 associates with p59 fyn , a Src family kinase known to phosphorylate p125FAK. The identification of a signaling pathway initiated by CD146 engagement and which includes p59 fyn , p125FAK, and paxillin indicates that CD146 participates in outside-in signaling in endothelial cells.

Multifaceted roles of MHC class I and MHC class I–like molecules in T cell activation

In addition to the TCR and classical MHC class I, MHC class 1–like molecules can interact with a variety of receptors that play a role in T cell activation. Engagement of NKG2D on CMV-specific αβ CD8+ cells by MIC was found to provide them with a costimulatory signal and augment their cytotoxic response.

Thérapies antitumorales par ciblage des cellules Natural Killer

Les cellules NK expriment un repertoire de recepteurs qui leur permettent de detecter les cellules cancereuses tout en epargnant les cellules normales. Ces cellules peuvent etre stimulees ou reactivees par differentes strategies therapeutiques qui sont presentees dans cet articlexa0: utilisation de cellules NK allogeniques ou autologues genetiquement modifiees, utilisation d’anticorps inhibant les recepteurs inhibiteurs des cellules NK (points de controle immunitaire), utilisation de cytokines activant les cellules NK, etc.