Abstract
Purpose
The purpose of this study was to quantify and characterize peripheral blood regulatory T cells (Tregs), as well as the IL-10 plasma concentration, in Masters athletes at rest and after an acute exhaustive exercise test.
Methods
Eighteen Masters athletes (self-reported training: 24.6 ± 1.83 years; 10.27 ± 0.24 months and 5.45 ± 0.42 h/week per each month trained) and an age-matched control group of ten subjects (that never took part in regular physical training) volunteered for this study. All subjects performed an incremental test to exhaustion on a cycle ergometer. Blood samples were obtained before (Pre), 10 min into recovery (Post), and 1 h after the test (1 h).
Results
Absolute numbers of Tregs were similar in both groups at rest. Acute exercise induced a significant increase in absolute numbers of Tregs at Post (0.049 ± 0.021 to 0.056 ± 0.024 × 109/L, P = 0.029 for Masters; 0.048 ± 0.017 to 0.058 ± 0.020 × 109/L, P = 0.037 for control) in both groups. Treg mRNA expression for FoxP3, IL-10, and TGF-β in sorted Tregs was similar throughout the trials in both groups. Masters athletes showed a higher percentage of subjects expressing the FoxP3 (100% for Masters vs. 78% for Controls, P = 0.038) and TGF-β (89% for Masters vs. 56% for Controls, P = 0.002) after exercise and a higher plasma IL-10 concentration (15.390 ± 7.032 for Masters vs. 2.411 ± 1.117 for control P = 0.001, ES = 2.57) at all timepoints. KLRG1 expression in Tregs was unchanged.
Conclusion
Our findings showed that Masters athletes have elevated anti-inflammatory markers and maintain the number of Tregs, and may be an adaptive response to lifelong training.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Abbreviations
- 1 h:
-
1 h post-exercise
- APCs:
-
Antigen-presenting cells
- KLRG1:
-
Killer cell lectin-like receptor G1
- IL:
-
Interleukin
- Pre:
-
Before exercise
- Post:
-
10 min into recovery
- VO2max :
-
Maximal oxygen consumption
- URTI:
-
Upper respiratory tract infection
- Tregs:
-
Regulatory T cells
References
Beyersdorf N, Ding X, Tietze JK, Hanke T (2007) Characterization of mouse CD4 T cell subsets defined by expression of KLRG1. Eur J Immunol 37:3445–3454. doi:10.1002/eji.200737126
Booth NJ, McQuaid AJ, Sobande T et al (2010) Different proliferative potential and migratory characteristics of human CD4+ regulatory T cells that express either CD45RA or CD45RO. J Immunol 184:4317–4326. doi:10.4049/jimmunol.0903781
Campbell DJ, Ziegler SF (2007) FOXP3 modifies the phenotypic and functional properties of regulatory T cells. Nat Rev Immunol 7:305–310. doi:10.1038/nri2061
Chodzko-Zajko WJ, Proctor DN, Fiatarone Singh M a et al (2009) American College of Sports Medicine position stand. Exercise and physical activity for older adults. Med Sci Sports Exerc 41:1510–1530. doi:10.1249/MSS.0b013e3181a0c95c
Corthay A (2009) How do regulatory T cells work? Scand J Immunol 70:326–336. doi:10.1111/j.1365-3083.2009.02308.x
Cosgrove C, Galloway SDR, Neal C et al (2012) The impact of 6-month training preparation for an Ironman triathlon on the proportions of naive, memory and senescent T cells in resting blood. Eur J Appl Physiol 112:2989–2998. doi:10.1007/s00421-011-2273-9
de Araújo AL, Silva LCR, Fernandes JR, Benard G (2013) Preventing or reversing immunosenescence: can exercise be an immunotherapy? Immunotherapy 5:879–893. doi:10.2217/imt.13.77
de Moura Braz SC, de Melo AS, da Glória Aureliano de Melo Cavalca M et al (2014) Increase in the expression of CD4+ CD25+ lymphocytic T cells in the indeterminate clinical form of human chagas disease after stimulation with recombinant antigens of Trypanosoma cruzi. J Clin Immunol 34:991–998. doi:10.1007/s10875-014-0092-6
Fehérvari Z, Sakaguchi S (2004) CD4+ Tregs and immune control. J Clin Invest 114:1209–1217. doi:10.1172/JCI23395
Fessler J, Ficjan A, Duftner C, Dejaco C (2013) The impact of aging on regulatory T-cells. Front Immunol 4:1–6. doi:10.3389/fimmu.2013.00231
Fu S, Zhang N, Yopp AC et al (2004) TGF-beta induces Foxp3+ T-regulatory cells from CD4+ CD25—precursors. Am J Transplant 4:1614–1627. doi:10.1111/j.1600-6143.2004.00566.x
Fujio K, Okamura T, Yamamoto K (2010) The Family of IL-10-secreting CD4+ T cells. Adv Immunol 105:99–130. doi:10.1016/S0065-2776(10)05004-2
Gleeson M (2007) Immune function in sport and exercise. J Appl Physiol 103:693–699. doi:10.1152/japplphysiol.00008.2007
Gleeson M, Walsh NP (2012) The BASES expert statement on exercise, immunity, and infection. J Sports Sci 30:321–324. doi:10.1080/02640414.2011.627371
Gleeson M, Bishop NC, Stensel DJ et al (2011) The anti-inflammatory effects of exercise: mechanisms and implications for the prevention and treatment of disease. Nat Rev Immunol 11:607–615. doi:10.1038/nri3041
Gleeson M, Bishop N, Oliveira M, et al (2012) Respiratory infection risk in athletes: association with antigen-stimulated IL-10 production and salivary IgA secretion. Scand J Med Sci Sport 22:410–417. doi:10.1111/j.1600-0838.2010.01272.x
Handzlik MK, Shaw AJ, Dungey M et al (2013) 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 113:1839–1848. doi:10.1007/s00421-013-2614-y
Henson SM, Akbar AN (2009) KLRG1–more than a marker for T cell senescence. Age 31:285–291. doi:10.1007/s11357-009-9100-9
Hwang K-A, Kim H-R, Kang I (2009) Aging and human CD4(+) regulatory T cells. Mech Ageing Dev 130:509–517. doi:10.1016/j.mad.2009.06.003
Jagger A, Shimojima Y, Goronzy JJ, Weyand CM (2014) Regulatory T cells and the immune aging process: a mini-review. Gerontology 60:130–137. doi:10.1159/000355303
Lages CS, Suffia I, Velilla PA et al (2008) Functional regulatory T cells accumulate in aged hosts and promote chronic infectious disease reactivation. J Immunol 181:1835–1848
Littwitz-Salomon E, Akhmetzyanova I, Vallet C, et al (2015) Activated regulatory T cells suppress effector NK cell responses by an IL-2-mediated mechanism during an acute retroviral infection. Retrovirology 12:66. doi:10.1186/s12977-015-0191-3
Liu W, Putnam AL, Xu-Yu Z et al (2006) CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ T reg cells. J Exp Med 203:1701–1711. doi:10.1084/jem.20060772
Lowder T, Dugger K, Deshane J et al (2010) Repeated bouts of aerobic exercise enhance regulatory T cell responses in a murine asthma model. Brain Behav Immun 24:153–159. doi:10.1016/j.bbi.2009.09.011
Miyara M, Yoshioka Y, Kitoh A et al (2009) Functional delineation and differentiation dynamics of human CD4+ T cells expressing the FoxP3 transcription factor. Immunity 30:899–911. doi:10.1016/j.immuni.2009.03.019
Nieman DC, Johanssen LM, Lee JW (1989) Infectious episodes in runners before and after a roadrace. J Sports Med Phys Fitness 29:289–296
Perry C, Pick M, Bdolach N et al (2013) Endurance exercise diverts the balance between Th17 cells and regulatory T cells. PLoS One 8:1–8. doi:10.1371/journal.pone.0074722
Pollock RD, Carter S, Velloso CP et al (2015) An investigation into the relationship between age and physiological function in highly active older adults. J Physiol 593:657–680. doi:10.1113/jphysiol.2014.282863
Sakaguchi S, Miyara M, Costantino CM, Hafler DA (2010) FOXP3+ regulatory T cells in the human immune system. Nat Rev Immunol 10:490–500. doi:10.1038/nri2785
Schmidt A, Oberle N, Krammer PH (2012) Molecular mechanisms of treg-mediated T cell suppression. Front Immunol 3:51. doi:10.3389/fimmu.2012.00051
Silva LCR, de Araújo AL, Fernandes JR, et al (2016) Moderate and intense exercise lifestyles attenuate the effects of aging on telomere length and the survival and composition of T cell subpopulations. Age (Omaha) 38:1–16. doi:10.1007/s11357-016-9879-0
Simpson RJ, Lowder TW, Spielmann G et al (2012) Exercise and the aging immune system. Ageing Res Rev 11:404–420. doi:10.1016/j.arr.2012.03.003
Simpson RJ, Kunz H, Agha N, Graff R (2015) Exercise and the regulation of immune functions. Prog Mol Biol Transl Sci 135:355–380. doi:10.1016/bs.pmbts.2015.08.001
Tanaka H, Seals DR (2008) Endurance exercise performance in Masters athletes: age-associated changes and underlying physiological mechanisms. J Physiol 586:55–63. doi:10.1113/jphysiol.2007.141879
Tauro S, Nguyen P, Li B, Geiger TL (2013) Diversification and senescence of Foxp3+ regulatory T cells during experimental autoimmune encephalomyelitis. Eur J Immunol 43:1195–1207. doi:10.1002/eji.201242881
Teixeira AM, Rama L, Carvalho HM, et al (2014) Changes in naïve and memory T-cells in elite swimmers during a winter training season. Brain Behav Immun 39:186–193. doi:10.1016/j.bbi.2014.01.002
Tossige-Gomes R, Ottone VO, Oliveira PN et al (2014) Leukocytosis, muscle damage and increased lymphocyte proliferative response after an adventure sprint race. Braz J Med Biol Res 0:000–000. doi:10.1590/1414-431X20143187
Uchiyama M, Jin X, Yin E et al (2015) Treadmill exercise induces murine cardiac allograft survival and generates regulatory T cell. Transpl Int 28:352–362. doi:10.1111/tri.12491
van der Geest KSM, Abdulahad WH, Tete SM et al (2014) Aging disturbs the balance between effector and regulatory CD4+ T cells. Exp Gerontol 60:190–196. doi:10.1016/j.exger.2014.11.005
Wang J, Song H, Tang X, et al (2012) Effect of exercise training intensity on murine T-regulatory cells and vaccination response. Scand J Med Sci Sport 22:643–652. doi:10.1111/j.1600-0838.2010.01288.x
Yeh S-H, Chuang H, Lin L-W et al (2006) Regular tai chi chuan exercise enhances functional mobility and CD4CD25 regulatory T cells. Br J Sports Med 40:239–243. doi:10.1136/bjsm.2005.022095
Yeh S-H, Chuang H, Lin L-W et al (2009) Regular Tai Chi Chuan exercise improves T cell helper function of patients with type 2 diabetes mellitus with an increase in T-bet transcription factor and IL-12 production. Br J Sports Med 43:845–850. doi:10.1136/bjsm.2007.043562
Yoshimura A, Wakabayashi Y, Mori T (2010) Cellular and molecular basis for the regulation of inflammation by TGF-beta. J Biochem 147:781–792. doi:10.1093/jb/mvq043
Acknowledgements
The authors would like to thank all the master athletes and others participants that volunteered to contribute in this study.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Funding
The study was funded by the Faculty of Sport Sciences and Physical Education, University of Coimbra. In addition, the present manuscript was accomplished with support from CAPES, Coordination for the Improvement of Higher Education Personnel, Brazil (LGM—Grants Number BEX-1417/13−4). AMT and LR are registered in the unit UID/DTP/04213/2016.
Conflict of interest
All authors declare no conflicts of interest.
Additional information
Communicated by William J. Kraemer.
Rights and permissions
About this article
Cite this article
Minuzzi, L.G., Rama, L., Bishop, N.C. et al. Lifelong training improves anti-inflammatory environment and maintains the number of regulatory T cells in masters athletes. Eur J Appl Physiol 117, 1131–1140 (2017). https://doi.org/10.1007/s00421-017-3600-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00421-017-3600-6