Adaptive reconfiguration of the human NK-cell compartment in response to cytomegalovirus: a different perspective of the host-pathogen interaction

Eur J Immunol. 2013 May;43(5):1133-41. doi: 10.1002/eji.201243117.


As discussed in this review, human cytomegalovirus (HCMV) infection in healthy individuals is associated with a variable and persistent increase of NK cells expressing the CD94/NKG2C activating receptor. The expansion of NKG2C(+) NK cells reported in other infectious diseases is systematically associated with HCMV co-infection. The functionally mature NKG2C(bright) NK-cell subset expanding in HCMV(+) individuals displays inhibitory Ig-like receptors (KIR and LILRB1) specific for self HLA class I, and low levels of NKp46 and NKp30 activating receptors. Such reconfiguration of the NK-cell compartment appears particularly marked in immunocompromised patients and in children with symptomatic congenital infection, thus suggesting that its magnitude may be inversely related with the efficiency of the T-cell-mediated response. This effect of HCMV infection is reminiscent of the pattern of response of murine Ly49H(+) NK cells against murine CMV (MCMV), and it has been hypothesized that a cognate interaction of the CD94/NKG2C receptor with HCMV-infected cells may drive the expansion of the corresponding NK-cell subset. Yet, the precise role of NKG2C(+) cells in the control of HCMV infection, the molecular mechanisms underlying the NK-cell compartment redistribution, as well as its putative influence in the response to other pathogens and tumors remain open issues.

Publication types

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

MeSH terms

  • Adaptation, Physiological / immunology
  • Animals
  • Cell Proliferation
  • Child
  • Cytomegalovirus / immunology
  • Cytomegalovirus Infections / immunology*
  • Cytomegalovirus Infections / pathology
  • Cytomegalovirus Infections / virology
  • Gene Expression
  • Herpesviridae Infections / immunology*
  • Herpesviridae Infections / pathology
  • Herpesviridae Infections / virology
  • Host-Pathogen Interactions
  • Humans
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / pathology
  • Killer Cells, Natural / virology
  • Muromegalovirus / immunology
  • NK Cell Lectin-Like Receptor Subfamily C / genetics
  • NK Cell Lectin-Like Receptor Subfamily C / immunology*
  • NK Cell Lectin-Like Receptor Subfamily D / genetics
  • NK Cell Lectin-Like Receptor Subfamily D / immunology*
  • Receptors, Natural Killer Cell / genetics
  • Receptors, Natural Killer Cell / immunology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / pathology
  • T-Lymphocytes / virology


  • KLRC2 protein, human
  • KLRD1 protein, human
  • NK Cell Lectin-Like Receptor Subfamily C
  • NK Cell Lectin-Like Receptor Subfamily D
  • Receptors, Natural Killer Cell