Acute exercise preferentially redeploys NK-cells with a highly-differentiated phenotype and augments cytotoxicity against lymphoma and multiple myeloma target cells

Austin B. Bigley, Katayoun Rezvani, Claude Chew, Takuya Sekine, Mira Pistillo, Brian Crucian, Catherine M. Bollard, Richard J. Simpson

Research output: Contribution to journalArticlepeer-review

111 Scopus citations


NK-cells undergo a "licensing" process as they develop into fully-functional cells capable of efficiently killing targets. NK-cell differentiation is accompanied by an increased surface expression of inhibitory killer immunoglobulin-like receptor (KIR) molecules, which is positively associated with cytotoxicity against the HLA-deficient K562 cell line. NK-cells are rapidly redeployed between the blood and tissues in response to acute exercise, but it is not known if exercise evokes a preferential trafficking of differentiated NK-cells or impacts NK-cell cytotoxic activity (NKCA) against HLA-expressing target cells.Sixteen healthy cyclists performed three 30-min bouts of cycling exercise at -5%, +5%, and +15% of lactate threshold. Blood samples obtained before, immediately after, and 1. h after exercise were used to enumerate NK-cells and their subsets, and determine NKCA and degranulating subsets (CD107+) against cell lines of multiple myeloma (U266 and RPMI-8226), lymphoma (721.221 and 221 AEH), and leukemia (K562) origin by 4 and 10-color flow cytometry, respectively.Exercise evoked a stepwise redeployment of NK-cell subsets in accordance with differentiation status [highly-differentiated (KIR+/NKG2A-) >. medium-differentiated (KIR+/NKG2A+). >. low-differentiated (KIR-/NKG2A+)] that was consistent across all exercise intensities. NKCA per cell increased ~1.6-fold against U266 and 221 AEH targets 1. h post-exercise and was associated with a decreased proportion of NK-cells expressing the inhibitory receptor CD158b and increased proportion of NK-cells expressing the activating receptor NKG2C, respectively. We conclude that exercise evokes a preferential redeployment of NK-cell subsets with a high differentiation phenotype and augments cytotoxicity against HLA-expressing target cells. Exercise may serve as a simple strategy to enrich the blood compartment of highly cytotoxic NK-cell subsets that can be harvested for clinical use.

Original languageEnglish (US)
Pages (from-to)160-171
Number of pages12
JournalBrain, Behavior, and Immunity
StatePublished - Jul 2014
Externally publishedYes


  • 221 AEH
  • 721.221
  • Acute stress
  • CD158
  • CD57
  • Exercise immunology
  • K562
  • KLRG1
  • NKG2A
  • NKG2C
  • RPMI-8226
  • U266

ASJC Scopus subject areas

  • Immunology
  • Endocrine and Autonomic Systems
  • Behavioral Neuroscience

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