Cutting edge: CD8+ T cell priming in the absence of NK cells leads to enhanced memory responses

J Immunol. 2011 Mar 15;186(6):3304-8. doi: 10.4049/jimmunol.1004122. Epub 2011 Feb 9.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cells, Cultured
  • Coculture Techniques
  • Female
  • Humans
  • Immunologic Memory* / genetics
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism
  • Killer Cells, Natural / pathology
  • Lymphocyte Activation / genetics
  • Lymphocyte Activation / immunology*
  • Lymphocyte Depletion / methods*
  • Melanoma, Experimental / immunology
  • Melanoma, Experimental / metabolism
  • Melanoma, Experimental / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • NK Cell Lectin-Like Receptor Subfamily K / deficiency
  • NK Cell Lectin-Like Receptor Subfamily K / metabolism
  • NK Cell Lectin-Like Receptor Subfamily K / physiology
  • Perforin
  • Pore Forming Cytotoxic Proteins / biosynthesis
  • Pore Forming Cytotoxic Proteins / genetics
  • Pore Forming Cytotoxic Proteins / physiology
  • Up-Regulation / genetics
  • Up-Regulation / immunology*

Substances

  • Klrk1 protein, mouse
  • NK Cell Lectin-Like Receptor Subfamily K
  • PRF1 protein, human
  • Pore Forming Cytotoxic Proteins
  • Perforin