Self MHC class I-licensed NK cells enhance adaptive CD8 T-cell viral immunity

Blood. 2011 May 12;117(19):5133-41. doi: 10.1182/blood-2010-12-324632. Epub 2011 Mar 23.

Abstract

MHC class I (MHC I) is essential to NK- and T-cell effector and surveillance functions. However, it is unknown whether MHC I polymorphism influences adaptive immunity through NK cells. Previously, we found that MHC I D(k), a cognate ligand for the Ly49G2 inhibitory receptor, was essential to NK control of murine (M)CMV infection. Here we assessed the significance of NK inhibitory receptor recognition of MCMV on CD8 T cells in genetically defined MHC I D(k) disparate mice. We observed that D(k)-licensed Ly49G2⁺ NK cells stabilized and then enhanced conventional dendritic cells (cDCs) recovery after infection. Furthermore, licensed NK support of cDC recovery was essential to enhance the tempo, magnitude, and effector activity of virus-specific CD8 T cells. Minimal cDC and CD8 T-cell number differences after low-dose MCMV in D(k) disparate animals further implied that licensed NK recognition of MCMV imparted qualitative cDC changes to enhance CD8 T-cell priming.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adaptive Immunity / genetics
  • Adaptive Immunity / immunology*
  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Separation
  • Cytotoxicity, Immunologic / genetics
  • Cytotoxicity, Immunologic / immunology*
  • Dendritic Cells / immunology
  • Flow Cytometry
  • Genotype
  • HLA-D Antigens / genetics
  • HLA-D Antigens / immunology
  • Herpesviridae Infections / genetics
  • Herpesviridae Infections / immunology
  • Histocompatibility Antigens Class I / genetics*
  • Histocompatibility Antigens Class I / immunology
  • Killer Cells, Natural / immunology*
  • Lymphocyte Activation / genetics
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Muromegalovirus / immunology
  • NK Cell Lectin-Like Receptor Subfamily A / immunology
  • Polymorphism, Genetic

Substances

  • HLA-D Antigens
  • Histocompatibility Antigens Class I
  • NK Cell Lectin-Like Receptor Subfamily A