Murine CXCR3+CD27bright NK cells resemble the human CD56bright NK-cell population

Eur J Immunol. 2010 May;40(5):1428-39. doi: 10.1002/eji.200940056.

Abstract

Human NK cells can be subdivided into CD56(dim) and CD56(bright) NK cells, which exhibit different phenotypical and functional characteristics. As murine NK cells lack CD56 or a distinct correlate, direct comparative studies of NK cells in mice and humans are limited. Although CD27 is currently proposed as a feasible subset marker in mice, we assume that the usage of this marker alone is insufficient. We rather investigated the expression of the chemokine receptor CXCR3 for its suitability for distinguishing murine NK-cell subsets with simultaneous consideration of CD27. Compared with CXCR3(-) NK cells, exerting stronger cytotoxic capability, CXCR3+ NK cells displayed an activated phenotype with a lower expression of Ly49 receptors, corresponding to human CD56(bright) NK cells. Also in common with human CD56(bright) NK cells, murine CXCR3+ NK cells exhibit prolific expansion as well as robust IFN-gamma, TNF-alpha and MIP-1alpha production. We additionally demonstrated changes in both CXCR3 and CD27 expression upon NK-cell activation. In summary, CXCR3 serves as an additional applicable marker for improved discrimination of functionally distinct murine NK-cell subsets that comply with those in humans.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers
  • CD56 Antigen / analysis*
  • Chemokine CCL3 / biosynthesis
  • Chemokine CCL3 / genetics
  • Chemokine CCL3 / metabolism
  • Cytotoxicity, Immunologic
  • Female
  • Humans
  • Immunophenotyping
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / genetics
  • Interferon-gamma / metabolism
  • Interleukins / pharmacology
  • Ionomycin / pharmacology
  • Killer Cells, Natural / chemistry
  • Killer Cells, Natural / classification*
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism
  • Lymphocyte Activation / drug effects
  • Lymphocyte Subsets / chemistry*
  • Lymphocyte Subsets / immunology
  • Lymphocyte Subsets / metabolism
  • Mice
  • Mice, Inbred C57BL
  • NK Cell Lectin-Like Receptor Subfamily A / analysis
  • RNA, Messenger / biosynthesis
  • Receptors, CXCR3 / analysis*
  • Species Specificity
  • Specific Pathogen-Free Organisms
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / analysis*
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Biomarkers
  • CD56 Antigen
  • Ccl3 protein, mouse
  • Chemokine CCL3
  • Cxcr3 protein, mouse
  • Interleukins
  • NK Cell Lectin-Like Receptor Subfamily A
  • RNA, Messenger
  • Receptors, CXCR3
  • Tumor Necrosis Factor Receptor Superfamily, Member 7
  • Tumor Necrosis Factor-alpha
  • Ionomycin
  • Interferon-gamma