Latent cytomegalovirus infection enhances anti-tumour cytotoxicity through accumulation of NKG2C+ NK cells in healthy humans

A. B. Bigley, K. Rezvani, N. Shah, T. Sekine, N. Balneger, M. Pistillo, N. Agha, H. Kunz, D. P. O'Connor, C. M. Bollard, R. J. Simpson

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

Cytomegalovirus (CMV) infection markedly expands NKG2C+/NKG2A− NK cells, which are potent killers of infected cells expressing human leucocyte antigen (HLA)-E. As HLA-E is also over-expressed in several haematological malignancies and CMV has been linked to a reduced risk of leukaemic relapse, we determined the impact of latent CMV infection on NK cell cytotoxicity against four tumour target cell lines with varying levels of HLA-E expression. NK cell cytotoxicity against K562 (leukaemia origin) and U266 (multiple myeloma origin) target cells was strikingly greater in healthy CMV-seropositive donors than seronegative donors and was associated strongly with target cell HLA-E and NK cell NKG2C expression. NK cell cytotoxicity against HLA-E transfected lymphoma target cells (221.AEH) was ∼threefold higher with CMV, while NK cell cytotoxicity against non-transfected 721.221 cells was identical between the CMV groups. NK cell degranulation (CD107a+) and interferon (IFN)-γ production to 221.AEH cells was localized almost exclusively to the NKG2C subset, and antibody blocking of NKG2C completely eliminated the effect of CMV on NK cell cytotoxicity against 221.AEH cells. Moreover, 221.AEH feeder cells and interleukin (IL)−15 were found to expand NKG2C+/NKG2A NK cells preferentially from CMV-seronegative donors and increase NK cell cytotoxicity against HLA-E+ tumour cell lines. We conclude that latent CMV infection enhances NK cell cytotoxicity through accumulation of NKG2C+ NK cells, which may be beneficial in preventing the initiation and progression of haematological malignancies characterized by high HLA-E expression.

Original languageEnglish (US)
Pages (from-to)239-251
Number of pages13
JournalClinical and Experimental Immunology
Volume185
Issue number2
DOIs
StatePublished - Aug 1 2016
Externally publishedYes

Keywords

  • 221 AEH
  • CD158
  • CD57
  • K562
  • NKG2A
  • U266
  • leukaemia
  • lymphoma
  • multiple myeloma

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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