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Int J Sports Med 2024; 45(03): 211-221
DOI: 10.1055/a-2197-0882
Physiology & Biochemistry

HIIT Induces Stronger Shifts within the Peripheral T Cell Compartment Independent of Sex

Sebastian Proschinger
1   Division of Performance and Health (Sports Medicine), TU Dortmund University, Institute for Sport and Sport Science, Dortmund, Germany
,
Alexander Schenk
1   Division of Performance and Health (Sports Medicine), TU Dortmund University, Institute for Sport and Sport Science, Dortmund, Germany
,
Alan J. Metcalfe
2   Department for Molecular and Cellular Sports Medicine, Institute of Cardiovascular Research and Sports Medicine, German Sport University Cologne, Cologne, Germany
,
Philipp Zimmer
1   Division of Performance and Health (Sports Medicine), TU Dortmund University, Institute for Sport and Sport Science, Dortmund, Germany
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Abstract

Acute exercise induces changes within the T-cell compartment, especially in cytotoxic CD8+ memory subsets, depending on exercise intensity and duration. It is unclear whether exercise-induced changes in major T-cell subsets differ in response to acute high-intensity interval training (HIIT) or moderate-intensity continuous training (MICT) and whether sex-specific effects exist. Twenty-four recreationally active runners (females: n=12, 27.8±4.1years, 54.4±4.6 ml*kg-1*min-1; males: n=12, 31.6±3.8years, 58.9±7.7 ml*kg-1*min-1) participated in this randomized controlled crossover study, and conducted an energy- and duration-matched HIIT and MICT session. Blood was sampled before (T1), immediately (T2) and 1 h after exercise (T3). Flow cytometry was used to identify T-cell populations. HIIT decreased the proportion of CD8+ T-cells more pronounced at T3 compared to MICT (p=0.007), induced a significantly stronger increase in the CD8+ effector memory (TEM) cell proportion at T2 (p=0.032), and decreased CD4+ central memory proportion more pronounced at T2 (p=0.029). A decrease below baseline CD8+ TEM proportion at T3 was observed only after HIIT (p<0.001). No interaction effects between sexes were revealed. Taken together, HIIT represents a more potent stimulus to induce shifts mainly within the cytotoxic CD8+ T-cell compartment, thereby giving implications to investigate the role of HIIT on the cell´s effector phenotype and function in more detail.

Key words

high-intensity interval training - T cells - gender - acute exercise - randomized controlled trial

Supplementary Material



Publication History

Received: 26 April 2023

Accepted: 12 October 2023

Article published online:
22 December 2023

© 2023. Thieme. All rights reserved.

Georg Thieme Verlag
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Jameson SC, Masopust D. Understanding Subset Diversity in T Cell Memory. Immunity 2018; 48: 214-226
    CrossrefPubMedSearch in Google Scholar
  • 2 Martin MD, Badovinac VP. Defining memory CD8 T cell. Front Immunol 2018; 9: 2692
    CrossrefPubMedSearch in Google Scholar
  • 3 Geginat J, Lanzavecchia A, Sallusto F. Proliferation and differentiation potential of human CD8+ memory T-cell subsets in response to antigen or homeostatic cytokines. Blood 2003; 101: 4260-4266
    CrossrefPubMedSearch in Google Scholar
  • 4 Krüger K, Alack K, Ringseis R. et al. Apoptosis of T-Cell Subsets after Acute High-Intensity Interval Exercise. Med Sci Sports Exerc 2016; 48: 2021-2029
    CrossrefPubMedSearch in Google Scholar
  • 5 Campbell JP, Riddell NE, Burns VE. et al. Acute exercise mobilises CD8+ T lymphocytes exhibiting an effector-memory phenotype. Brain Behav Immun 2009; 23: 767-775
    CrossrefPubMedSearch in Google Scholar
  • 6 Graff RM, Kunz HE, Agha NH. et al. β2-Adrenergic receptor signaling mediates the preferential mobilization of differentiated subsets of CD8+ T-cells, NK-cells and non-classical monocytes in response to acute exercise in humans. Brain Behav Immun 2018; 74: 143-153
    CrossrefPubMedSearch in Google Scholar
  • 7 Gustafson MP, Wheatley-Guy CM, Rosenthal AC. et al. Exercise and the immune system: Taking steps to improve responses to cancer immunotherapy. J Immunother Cancer 2021; 9: e001872
    CrossrefPubMedSearch in Google Scholar
  • 8 Pedersen L, Idorn M, Olofsson GH. et al. Voluntary running suppresses tumor growth through epinephrine- and IL-6-dependent NK cell mobilization and redistribution. Cell Metab 2016; 23: 554-562
    CrossrefPubMedSearch in Google Scholar
  • 9 Rundqvist H, Veliça P, Barbieri L. et al. Cytotoxic t-cells mediate exercise-induced reductions in tumor growth. Elife 2020; 9: 1-25
    CrossrefPubMedSearch in Google Scholar
  • 10 Gomes-Santos IL, Amoozgar Z, Kumar AS. et al. Exercise training improves tumor control by increasing CD8+ T-cell infiltration via CXCR3 signaling and sensitizes breast cancer to immune checkpoint blockade. Cancer Immunol Res 2021; 9: 765-778
    CrossrefPubMedSearch in Google Scholar
  • 11 Schenk A, Esser T, Belen S. et al. Distinct distribution patterns of exercise-induced natural killer cell mobilization into the circulation and tumor tissue of patients with prostate cancer. Am J Physiol Cell Physiol 2022; 323: 879-884
    CrossrefPubMedSearch in Google Scholar
  • 12 Simpson RJ, Katsanis E. The immunological case for staying active during the COVID-19 pandemic. Brain Behav Immun 2020; 87: 6-7
    CrossrefPubMedSearch in Google Scholar
  • 13 Duggal NA, Niemiro G, Harridge SDR. et al. Can physical activity ameliorate immunosenescence and thereby reduce age-related multi-morbidity?. Nat Rev Immunol 2019; 19: 563-572
    CrossrefPubMedSearch in Google Scholar
  • 14 Gleeson M. Immune function in sport and exercise. J Appl Physiol 2007; 103: 693-699
    CrossrefPubMedSearch in Google Scholar
  • 15 Zúñiga TM, Baker FL, Smith KA. et al. Acute exercise mobilizes NKT-like cells with a cytotoxic transcriptomic profile but does not augment the potency of cytokine-induced killer (CIK) cells. Front Immunol 2022; 13: 938106
    CrossrefPubMedSearch in Google Scholar
  • 16 Simpson RJ, Campbell JP, Gleeson M. et al. Can exercise affect immune function to increase susceptibility to infection?. Exerc Immunol Rev 2020; 26: 8-22
    PubMedSearch in Google Scholar
  • 17 Campbell JP, Turner JE. Debunking the myth of exercise-induced immune suppression: Redefining the impact of exercise on immunological health across the lifespan. Front Immunol 2018; 9: 648
    CrossrefPubMedSearch in Google Scholar
  • 18 Krüger K, Lechtermann A, Fobker M. et al. Exercise-induced redistribution of T lymphocytes is regulated by adrenergic mechanisms. Brain Behav Immun 2008; 22: 324-338
    CrossrefPubMedSearch in Google Scholar
  • 19 O’Carroll L, Wardrop B, Murphy RP. et al. Circulating angiogenic cell response to sprint interval and continuous exercise. Eur J Appl Physiol 2019; 119: 743-752
    CrossrefPubMedSearch in Google Scholar
  • 20 Gustafson MP, DiCostanzo AC, Wheatley CM. et al. A systems biology approach to investigating the influence of exercise and fitness on the composition of leukocytes in peripheral blood. J Immunother Cancer 2017; 5: 1-14
    CrossrefPubMedSearch in Google Scholar
  • 21 Thum JS, Parsons G, Whittle T. et al. High-intensity interval training elicits higher enjoyment than moderate intensity continuous exercise. PLoS One 2017; 12: e0166299
    CrossrefPubMedSearch in Google Scholar
  • 22 Bartlett JD, Close GL, Maclaren DPM. et al. High-intensity interval running is perceived to be more enjoyable than moderate-intensity continuous exercise: Implications for exercise adherence. J Sports Sci 2011; 29: 547-553
    CrossrefPubMedSearch in Google Scholar
  • 23 Milanović Z, Sporiš G, Weston M. Effectiveness of High-Intensity Interval Training (HIT) and Continuous Endurance Training for VO2max Improvements: A Systematic Review and Meta-Analysis of Controlled Trials. Sports Med 2015; 45: 1469-1481
    CrossrefPubMedSearch in Google Scholar
  • 24 Bhatia C, Kayser B. Preoperative high-intensity interval training is effective and safe in deconditioned patients with lung cancer: A randomized clinical trial. J Rehabil Med 2019; 51: 712-718
    CrossrefPubMedSearch in Google Scholar
  • 25 Khalafi M, Symonds ME. The impact of high-intensity interval training on inflammatory markers in metabolic disorders: A meta-analysis. Scand J Med Sci Sports 2020; 30: 2020-2036
    CrossrefPubMedSearch in Google Scholar
  • 26 Ramos JS, Dalleck LC, Tjonna AE. et al. The Impact of High-Intensity Interval Training Versus Moderate-Intensity Continuous Training on Vascular Function: A Systematic Review and Meta-Analysis. Sports Med 2015; 45: 679-692
    CrossrefPubMedSearch in Google Scholar
  • 27 Wadley AJ, Cullen T, Vautrinot J. et al. High intensity interval exercise increases the frequency of peripheral PD-1+ CD8+ central memory T-cells and soluble PD-L1 in humans. Brain Behav Immun Health 2020; 3: 100049
    CrossrefPubMedSearch in Google Scholar
  • 28 Arroyo E, Tagesen EC, Hart TL. et al. Comparison of the lymphocyte response to interval exercise versus continuous exercise in recreationally trained men. Brain Behav Immun Health 2022; 20: 100415
    CrossrefPubMedSearch in Google Scholar
  • 29 Cowley ES, Olenick AA, McNulty KL. et al. “Invisible Sportswomen”: The Sex Data Gap in Sport and Exercise Science Research. Women Sport Phys Act J 2021; 29: 146-151
    CrossrefPubMedSearch in Google Scholar
  • 30 Schlagheck ML, Walzik D, Joisten N. et al. Cellular immune response to acute exercise: Comparison of endurance and resistance exercise. Eur J Haematol 2020; 105: 75-84
    CrossrefPubMedSearch in Google Scholar
  • 31 Handzlik MK, Shaw AJ, Dungey M. et al. The influence of exercise training status on antigen-stimulated IL-10 production in whole blood culture and numbers of circulating regulatory T cells. Eur J Appl Physiol 2013; 113: 1839-1848
    CrossrefPubMedSearch in Google Scholar
  • 32 Rumpf C, Proschinger S, Schenk A. et al. The Effect of Acute Physical Exercise on NK-Cell Cytolytic Activity: A Systematic Review and Meta-Analysis. Sports Med 2021; 51: 519-530
    CrossrefPubMedSearch in Google Scholar
  • 33 Klein SL, Flanagan KL. Sex differences in immune responses. Nat Rev Immunol 2016; 16: 626-638
    CrossrefPubMedSearch in Google Scholar
  • 34 Jones AM, Doust JH. A 1% treadmill grade most accurately reflects the energetic cost of outdoor running. J Sports Sci 1996; 14: 321-327
    CrossrefPubMedSearch in Google Scholar
  • 35 Yoon BK, Kravitz L, Robergs R. V̇O2max, protocol duration, and the V̇O2 plateau. Med Sci Sports Exerc 2007; 39: 1186-1192
    CrossrefPubMedSearch in Google Scholar
  • 36 Gilman MB. The Use of Heart Rate to Monitor the Intensity of Endurance Training. Sports Med 1996; 21: 73-79
    CrossrefPubMedSearch in Google Scholar
  • 37 Borg GA. Psychophysical bases of perceived exertion. Med Sci Sports Exerc 1982; 14: 377-381
    PubMedSearch in Google Scholar
  • 38 Scott NW, Mcpherson GC, Ramsay CR. et al. The method of minimization for allocation to clinical trials: A review. Control Clin Trials 2002; 23: 662-674
    CrossrefPubMedSearch in Google Scholar
  • 39 Bartlett JD, Joo CH, Jeong TS. et al. Matched work high-intensity interval and continuous running induce similar increases in PGC-1α mRNA, AMPK, p38, and p53 phosphorylation in human skeletal muscle. J Appl Physiol 2012; 112: 1135-1143
    CrossrefPubMedSearch in Google Scholar
  • 40 Zouhal H, Jacob C, Delamarche P. et al. Catecholamines and the effects of exercise, training and gender. Sports Med 2008; 38: 401-423
    CrossrefPubMedSearch in Google Scholar
  • 41 Fan X, Wang Y. β2 Adrenergic receptor on T lymphocytes and its clinical implications. Progress in Natural Science 2009; 19: 17-23
    CrossrefPubMedSearch in Google Scholar
  • 42 Farber DL, Yudanin NA, Restifo NP. Human memory T cells: Generation, compartmentalization and homeostasis. Nat Rev Immunol 2014; 14: 24-35
    CrossrefPubMedSearch in Google Scholar
  • 43 Verma K, Ogonek J, Varanasi PR. et al. Human CD8+ CD57- TEMRA cells: Too young to be called “old.”. PLoS One 2017; 12: e0177405
    CrossrefPubMedSearch in Google Scholar
  • 44 Krüger K, Mooren FC. Exercise-induced leukocyte apoptosis. Exerc Immunol Rev 2014; 20: 117-134
    PubMedSearch in Google Scholar
  • 45 Dhabhar FS, Malarkey WB, Neri E. et al. Stress-induced redistribution of immune cells-From barracks to boulevards to battlefields: A tale of three hormones – Curt Richter Award Winner. Psychoneuroendocrinology 2012; 37: 1345-1368
    CrossrefPubMedSearch in Google Scholar
  • 46 Hoffman-Goetz L, Pedersen BK. Exercise and the immune system: A model of the stress response?. Immunol Today 1994; 382-387
    CrossrefPubMedSearch in Google Scholar
  • 47 Mueller SN, Gebhardt T, Carbone FR. et al. Memory T cell subsets, migration patterns, and tissue residence. Annu Rev Immunol 2013; 31: 137-161
    CrossrefPubMedSearch in Google Scholar
  • 48 Rosato PC, Beura LK, Masopust D. Tissue resident memory T cells and viral immunity. Curr Opin Virol 2017; 22: 44-50
    CrossrefPubMedSearch in Google Scholar
  • 49 Schenkel JM, Fraser KA, Vezys V. et al. Sensing and alarm function of resident memory CD8+ T cells. Nat Immunol 2013; 14: 509-513
    CrossrefPubMedSearch in Google Scholar
  • 50 Dunne PJ, Faint JM, Gudgeon NH. et al. Epstein-Barr virus-specific CD8+ T cells that re-express CD45RA are apoptosis-resistant memory cells that retain replicative potential. Blood 2002; 100: 933-940
    CrossrefPubMedSearch in Google Scholar
  • 51 Pangrazzi L, Naismith E, Meryk A. et al. Increased IL-15 production and accumulation of highly differentiated CD8+ effector/memory T cells in the bone marrow of persons with cytomegalovirus. Front Immunol 2017; 8: 715
    CrossrefPubMedSearch in Google Scholar
  • 52 Neidleman J, Luo X, Frouard J. et al. SARS-CoV-2-Specific T Cells Exhibit Phenotypic Features of Helper Function, Lack of Terminal Differentiation, and High Proliferation Potential. Cell Rep Med 2020; 1: 100081
    CrossrefPubMedSearch in Google Scholar
  • 53 Champagne P, Ogg GS, King AS. et al. Skewed maturation of memory HIV-specific CD8 T lymphocytes. Nature 2001; 410: 106-111
    CrossrefPubMedSearch in Google Scholar
  • 54 Van Braeckel-Budimir N, Varga SM, Badovinac VP. et al. Repeated Antigen Exposure Extends the Durability of Influenza-Specific Lung-Resident Memory CD8+ T Cells and Heterosubtypic Immunity. Cell Rep 2018; 24: 3374-3382
    CrossrefPubMedSearch in Google Scholar
  • 55 Roberts AD, Woodland DL. Cutting Edge: Effector Memory CD8+ T Cells Play a Prominent Role in Recall Responses to Secondary Viral Infection in the Lung. J Immunol 2004; 172: 6533-6537
    CrossrefPubMedSearch in Google Scholar
  • 56 Gehad A, Teague JE, Matos TR. et al. A primary role for human central memory cells in tissue immunosurveillance. Blood Adv 2018; 2: 292-298
    CrossrefPubMedSearch in Google Scholar
  • 57 Landen S, Voisin S, Craig JM. et al. Genetic and epigenetic sex-specific adaptations to endurance exercise. Epigenetics 2019; 14: 523-535
    CrossrefPubMedSearch in Google Scholar
  • 58 Han J, Khatwani N, Searles TG. et al. Memory CD8+ T cell responses to cancer. Semin Immunol 2020; 49: 101435
    CrossrefPubMedSearch in Google Scholar
  • 59 Gillum TL, Kuennen MR, Schneider S. et al. A Review of Sex Differences in Immune Function after Aerobic Exercise. Exerc Immunol Rev 2011; 17: 104-121
    PubMedSearch in Google Scholar
  • 60 Timmons BW, Hamadeh MJ, Devries MC. et al. Influence of gender, menstrual phase, and oral contraceptive use on immunological changes in response to prolonged cycling. J Appl Physiol 2005; 99: 979-985
    CrossrefPubMedSearch in Google Scholar
  • 61 De La Fuente M, Martin MI, Ortega E. Changes in the phagocytic function of peritoneal macrophages from old mice after strenuous physical exercise. Comp lmmun Microbiol infect Dis 1990; 13: 189-198
    CrossrefPubMedSearch in Google Scholar
  • 62 Davis SN, Galassetti P, Wasserman DH. et al. Effects of Gender on Neuroendocrine and Metabolic Counterregulatory Responses to Exercise in Normal Man. J Clin Endocrinol Metab 2000; 85: 224-230
    PubMedSearch in Google Scholar
  • 63 Carter SL, Rennie C, Tarnopolsky MA. Substrate utilization during endurance exercise in men and women after endurance training. Am J Physiol Endocrinol Metab 2001; 280: 898-907
    CrossrefPubMedSearch in Google Scholar
  • 64 Simpson RJ, Bigley AB, Spielmann G. et al. Human cytomegalovirus infection and the immune response to exercise. Exerc Immunol Rev 2016; 22: 8-26
    PubMedSearch in Google Scholar
  • 65 Turner JE, Aldred S, Witard OC. et al. Latent Cytomegalovirus infection amplifies CD8 T-lymphocyte mobilisation and egress in response to exercise. Brain Behav Immun 2010; 24: 1362-1370
    CrossrefPubMedSearch in Google Scholar
  • 66 Mills PJ, Ziegler MG, Dimsdale JE. et al. Enumerative Immune Changes Following Acute Stress- Effect of the Menstrual Cycle. Brain Behav Immun 1995; 9: 190-195
    CrossrefPubMedSearch in Google Scholar
  • 67 Rooney BV, Bigley AB, LaVoy EC. et al. Lymphocytes and monocytes egress peripheral blood within minutes after cessation of steady state exercise: A detailed temporal analysis of leukocyte extravasation. Physiol Behav 2018; 194: 260-267
    CrossrefPubMedSearch in Google Scholar
  • 68 Minuzzi LG, Rama L, Bishop NC. et al. Lifelong training improves anti-inflammatory environment and maintains the number of regulatory T cells in masters athletes. Eur J Appl Physiol 2017; 117: 1131-1140
    CrossrefPubMedSearch in Google Scholar
  • 69 Simpson RJ, Kunz H, Agha N. et al. Exercise and the Regulation of Immune Functions. Prog Mol Biol Transl Sci 2015; 135: 355-380
    CrossrefPubMedSearch in Google Scholar
  • 70 Shek PN, Sabiston BH, Buguet A. et al. Strenuous Exercise and Immunological Changes: A Multiple-Time-Point Analysis of Leukocyte Subsets, CD4/CD8 Ratio, Immunoglobulin Production and NK Cell Response. Int J Sports Med 1995; 16: 466-474
    Thieme ConnectPubMedSearch in Google Scholar