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Brain Behav Immun. 2014 Jul;39:160-71. doi: 10.1016/j.bbi.2013.10.030. Epub 2013 Nov 5.

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

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Laboratory of Integrated Physiology, Department of Health and Human Performance, University of Houston, 3855 Holman Street, Houston, TX 77204, USA. Electronic address:
Department of Stem Cell Transplantation, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Laboratory of Integrated Physiology, Department of Health and Human Performance, University of Houston, 3855 Holman Street, Houston, TX 77204, USA.
Biomedical Research and Environmental Sciences Division, NASA Johnson Space Center, 2101 NASA Parkway, Houston, TX 77058, USA.
Center for Cell and Gene Therapy, Departments of Pediatrics, Medicine, and Pathology & Immunology, Baylor College of Medicine, Houston, TX 77030, USA.


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 1h 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 1h 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.


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

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