title: Cutting edge: CD8+ T cell priming in the absence of NK cells leads to enhanced memory responses.
abstract: It is uncertain whether NK cells modulate T cell memory differentiation. By using a genetic model that allows the selective depletion of NK cells, we show in this study that NK cells shape CD8(+) T cell fate by killing recently activated CD8(+) T cells in an NKG2D- and perforin-dependent manner. In the absence of NK cells, the differentiation of CD8(+) T cells is strongly biased toward a central memory T cell phenotype. Although, on a per-cell basis, memory CD8(+) T cells generated in the presence or the absence of NK cells have similar functional features and recall capabilities, NK cell deletion resulted in a significantly higher number of memory Ag-specific CD8(+) T cells, leading to more effective control of tumors carrying model Ags. The enhanced memory responses induced by the transient deletion of NK cells may provide a rational basis for the design of new vaccination strategies.
authors.affiliation: Medical Research Council Centre for Transplantation, King's College London, SE1 9RT London, United Kingdom.
authors.forename: Katrina
authors.initials: K
authors.lastname: Soderquest
authors.forename: Thierry
authors.initials: T
authors.lastname: Walzer
authors.forename: Biljana
authors.initials: B
authors.lastname: Zafirova
authors.forename: Linda S
authors.initials: LS
authors.lastname: Klavinskis
authors.forename: Bojan
authors.initials: B
authors.lastname: Polić
authors.forename: Eric
authors.initials: E
authors.lastname: Vivier
authors.forename: Graham M
authors.initials: GM
authors.lastname: Lord
authors.forename: Alfonso
authors.initials: A
authors.lastname: Martín-Fontecha
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D018920:Coculture Techniques; D005260:Female; D006801:Humans; D007156:Immunologic Memory / Q000235:genetics; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D008212:Lymphocyte Depletion / Q000379:methods*; D008546:Melanoma, Experimental / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000172:deficiency / Q000378:metabolism / Q000502:physiology; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology*
chemical_list: C527086:Klrk1 protein, mouse; D055655:NK Cell Lectin-Like Receptor Subfamily K; C510468:PRF1 protein, human; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin