Reciprocal age related change in natural killer cell receptors for MHC class I

Charles T. Lutz, Mikel B. Moore, Sarah Bradley, Brent J. Shelton, Susan K. Lutgendorf

Research output: Contribution to journalArticlepeer-review

82 Scopus citations


Natural killer (NK) cells are essential for healthy aging. NK cell activation is controlled by MHC class I-specific CD94/NKG2 receptors and killer immunoglobulin-like receptors (KIR). To assess NK cytotoxic function in isolation from MHC receptor engagement, we measured the ability of purified NK cells to kill mouse P815 target cells in the presence of anti-CD16 mAb. CD16-mediated cytotoxicity did not change with age, indicating that NK activation and cytotoxic granule release remained functional. We then investigated MHC class I receptor expression on NK cells. There was an age related decrease in CD94 and NKG2A expression and a reciprocal age related increase in KIR expression. NKG2A expression also declined with age on CD56 + T cells. CD94/NKG2A receptor function was proportional to expression, indicating that NK cell inhibitory signaling pathways were intact. NKG2A and KIR expression were complementary, suggesting that CD94/NKG2A function could substitute for inhibitory KIR function during polyclonal NK cell development in both young and elderly adults. The distinct roles of CD94/NKG2A and KIR receptors suggest that shifting MHC class I receptor expression patterns reflect age related changes in NK cell and CD56+ T cell turnover and function in vivo.

Original languageEnglish
Pages (from-to)722-731
Number of pages10
JournalMechanisms of Ageing and Development
Issue number6-7
StatePublished - Jun 2005

Bibliographical note

Funding Information:
This work was supported by NIH R01 DE11139, the Carver Foundation, the University of Iowa General Clinical Research Center, and the University of Kentucky Cancer Center. We thank Dr. Linda G. Snetselaar for help with study design, Colleen Fullenkamp and Dr. Phyllis Stumbo for help with donor recruitment and data collection, and Drs. Miguel López-Botet, Bice Perussia, and Marco Colonna for providing antibodies.


  • Aging
  • CD94
  • Cytotoxicity
  • KIR
  • MHC class I
  • NKG2A
  • NKT
  • Natural killer
  • Receptor

ASJC Scopus subject areas

  • Aging
  • Developmental Biology


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