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Evaluating the effects of exercise on Natural Killer cell cytotoxicity in pre- and post-pubertal boys and girls / Exercise and Natural Killer cell cytotoxicity in youth

Natural killer (NK) cells are a type of lymphocyte involved in innate and adaptive immunity. In adults, exercise can increase NK cell cytotoxicity both as a total percent of target cell lysis and an increase in the function of each NK cell. Much less is known about this response in children. Thus, the objectives of this study were to examine: 1) the effects of exercise intensity and structure on NK specific lysis and NKCA per cell in youth, and 2) differences in baseline and post-exercise specific lysis and NKCA per cell by pubertal status and sex. We also examined the NK cell and NK subset response to these exercise protocols by pubertal status and sex to help contextualize the NK functional response. We recruited healthy, recreationally active pre-pubertal (8-11 years, N=5) and late/post-pubertal (15-18 years, N=6) children from the Hamilton community. Participants completed 4 experimental cycling sessions in a randomized order including: high intensity intermittent (HI-INT) or continuous (HI-CONT), and moderate intensity intermittent (MOD-INT) or continuous (MOD-CONT) cycling. Blood was collected at baseline (PRE), immediately post-exercise (POST), and at 30- and 60-minutes recovery (REC1 and REC2, respectively). Peripheral Blood Mononuclear Cells (PBMC) were isolated from each timepoint and used in a cytotoxic assay with K562 targets. Flow cytometry was used to quantify target cell death (reported as specific lysis and NKCA per cell), and to determine NK cells and subsets as a proportion of lymphocytes. Exercise significantly increased specific lysis from PRE (25.1± 6.7%) to POST (30.6±11.0%), while NKCA per cell increased from PRE (0.69±0.76) to REC2 (1.3±1.3); p<0.05 for both. These responses were seen irrespective of exercise intensity and structure, pubertal status, and sex. The % total NK cells increased from PRE to POST (6.8±2.8% vs. 13.6±7.2%), and was greater in post-pubertal children vs. pre-pubertal children (20.9±6.2% vs. 9.1±4.3%), and after HI-INT (15.5±8.1%) and MOD-INT (16.2±9.5%) vs. HI-CONT (12.0 ± 5.0%) and MOD-CONT exercises (10.6 ± 4.5%; p<0.05 for all). Acute exercise can enhance NK cell cytotoxicity in youth regardless of exercise intensity, structure, pubertal status, or sex. NK function and mobilization responses to exercise did not always align, which suggests that unique post-exercise processes contribute to changes in NK cell proportions, specific lysis, and NKCA per cell. Our study has enhanced the understanding of exercise-induced changes NK cell cytotoxicity in the growing years. Future research will focus on explaining these effects, and exploring the clinical application of exercise programs in youth. / Thesis / Master of Science (MSc) / The purpose of this study was to determine if exercise can increase the function of Natural Killer cells (NK cells) in children. These cells are a very important part of our immune system that work to protect us from harmful infections and cancers. We also wanted to see if puberty or sex influence how NK cells respond to exercise. We asked boys and girls who were 8-11 years old or 15-18 years old to visit our lab 5 times. During their first visit, we measured their fitness level. In the next 4 visits, they completed one of four different types of exercise including: 1) 30 minutes of hard cycling, 2) 5 minutes of stop-and-start hard cycling, 3) 30 minutes of less hard cycling, and 4) 5 minutes of stop-and-start less hard cycling. We collected blood at four times during each session, including: 1) before the exercise, 2) immediately after the exercise, 3) 30-minutes after exercise, and 4) 60-minutes after exercise. We took NK cells from this blood and added them to cancer cells. We measured how many cancer cells were killed by the NK cells. We were interested in learning if exercise changed the percent of cancer cells killed by NK cells. We also wanted to know if exercise helped make each NK cell a better killer. We found that immediately after exercise, NK cells were able to kill a greater percent of cancer cells than they could before exercise. We also found that at 60-minutes after exercise, each NK cell killed a greater number of cancer cells than they were able to before exercise. There were no differences in NK cell cancer killing capacity between boys and girls, or between pre-pubertal or post-pubertal children. Our study helps us understand how we can increase important immune functions with exercise in children.

Identiferoai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/26700
Date January 2021
CreatorsHauck, Emily
ContributorsObeid, Joyce, Medical Sciences
Source SetsMcMaster University
LanguageEnglish
Detected LanguageEnglish
TypeThesis

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