Expansion of a unique CD57 +NKG2C hi natural killer cell subset during acute human cytomegalovirus infection

Sandra Lopez-Vergès, Jeffrey M. Milush, Brian S. Schwartz, Marcelo J. Pando, Jessica Jarjoura, Vanessa A. York, Jeffrey P. Houchins, Steve Miller, Sang Mo Kang, Phillip J. Norris, Douglas F. Nixon, Lewis L. Lanier

Research output: Contribution to journalArticle

419 Scopus citations

Abstract

During human CMV infection, there is a preferential expansion of natural killer (NK) cells expressing the activating CD94-NKG2C receptor complex, implicating this receptor in the recognition of CMV-infected cells. We hypothesized that NK cells expanded in response to pathogens will be marked by expression of CD57, a carbohydrate antigen expressed on highly mature cells within the CD56 dimCD16 + NK cell compartment. Here we demonstrate the preferential expansion of a unique subset of NK cells coexpressing the activating CD94-NKG2C receptor and CD57 in CMV + donors. These CD57 +NKG2C hi NK cells degranulated in response to stimulation through their NKG2C receptor. Furthermore, CD57 +NKG2C hiNK cells preferentially lack expression of the inhibitory NKG2A receptor and the inhibitory KIR3DL1 receptor in individuals expressing its HLA-Bw4 ligand. Moreover, in solid-organ transplant recipients with active CMV infection, the percentage of CD57 +NKG2C hi NK cells in the total NK cell population preferentially increased. During acute CMV infection, the NKG2C+ NK cells proliferated, became NKG2C hi, and finally acquired CD57. Thus, we propose that CD57 might provide a marker of "memory" NK cells that have been expanded in response to infection.

Original languageEnglish (US)
Pages (from-to)14725-14732
Number of pages8
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number36
DOIs
StatePublished - Sep 6 2011

Keywords

  • Innate immunity
  • Lymphocyte

ASJC Scopus subject areas

  • General

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    Lopez-Vergès, S., Milush, J. M., Schwartz, B. S., Pando, M. J., Jarjoura, J., York, V. A., Houchins, J. P., Miller, S., Kang, S. M., Norris, P. J., Nixon, D. F., & Lanier, L. L. (2011). Expansion of a unique CD57 +NKG2C hi natural killer cell subset during acute human cytomegalovirus infection. Proceedings of the National Academy of Sciences of the United States of America, 108(36), 14725-14732. https://doi.org/10.1073/pnas.1110900108