High-intensity interval training (HIT) has become an increasingly popular form of exercise because of its potentially large effects on exercise capacity and small time requirement for the past decade. It represents an exercise method that consists of alternating periods of high-intensity bouts of exercise and rest periods of low-intensity exercise. Originally used by athletes for training purposes, the rationale for its use is to increase training time spent at high intensities, thus producing a stronger stimulus for cardiovascular and muscular adaptations (6,40). Data suggest that HIT is superior to continuous (CONT) training for improving maximum oxygen consumption (V˙O2max) in athletes and young to middle-age adults (28,40). Recent studies demonstrated that patients also benefit from interval training modes. In this regard, HIT has been shown to improve peak oxygen uptake, quality of life, and cardiac remodeling in patients with cardiovascular and metabolic diseases (40).
Because exercise is known to be a strong modulator of the immune system, it has to be ensured that both patients and athletes do not affect their immune competence after training (22). Acute intensive bouts of exercise alter number and function of circulating cells (37). A lymphocytosis is observed during and immediately after exercise with numbers of T cells falling below preexercise levels during the early stages of recovery, before returning to resting values normally within 24 h. It is believed that lymphopenia is the result of an increase of at least two different processes. On the one hand, lymphocytes are redistributed into various tissues and organs (11). On the other hand, cells die by apoptosis (13,18). Although exercise of moderate intensities only marginally affects lymphocyte apoptosis, an increase of cell death was observed after several intensive types of exercise such as ultramarathon running (3), marathon running (18), and intensive treadmill running (18). Therefore, the role of apoptosis in the regulation of lymphocytes after acute HIT exercise is likely. To investigate the physiological role of apoptosis, the question about the underlying molecular mechanisms of lymphocyte apoptosis emerged. It was demonstrated that intensive exercise induces an increase of glucocorticoids, such as cortisol, and reactive oxygen species (ROS) mediate exercise-induced apoptosis (10,13). On the one hand, it is suggested that increased apoptosis is associated with a loss of immune competence. This idea is supported by studies that demonstrated a transient increase of upper respiratory tract infections after prolonged or intensive exercise (23). On the other hand, apoptosis is considered to be a regulatory mechanism to remove dysfunctional cells. In this regard, it was demonstrated that lymphocyte apoptosis induces the mobilization of hematopoietic progenitor cells (HPC), which might play a role in adaptation to regular training (13,19). However, to analyze potential detrimental or regulatory functions of lymphocyte apoptosis, it seems to be necessary to define the phenotype of lost cells more specifically. For that purpose, Simpson (30) noted that lymphocytes, which are mobilized into blood during exercise, are senescent cells that are known to be limited in their response against foreign antigens. Given that these particular cells mainly die by apoptosis, exercise-induced lymphocyte apoptosis might be a mechanism to delete mainly highly differentiated cells to expand the naive T-cell repertoire (30). Up to now, it is not quite clear which particular T-cell subtype is mainly affected by exercise. Besides more or less differentiated T cells, there are other T-cell subsets such as regulatory T cells (Tregs), which are suggested to have regulatory function on inflammatory processes (26). However, the effects of exercise on apoptosis of Tregs have been not investigated so far.
Therefore, the primary aim of this study was to compare T-cell mobilization and apoptosis after an acute HIT test and a continuous, moderate-intensity exercise test (CONT) matched for a similar energy expenditure and duration. In addition, progenitor cell mobilization, hormonal responses, and changes of potential apoptosis mediators were evaluated. We hypothesized that cellular responses such as mobilization and apoptosis of T-cell subpopulations are more pronounced after the HIT exercise and specifically targets highly differentiated T cells.
Twenty-three untrained male subjects were selected to participate in the study. The characteristics of these athletes can be found in Table 1. Inclusion criteria for this study required no participation in competitive sports, no more than 3 h regular sport activities per week, a V˙O2max below 55 mL·min−1·kg−1, and good physical health as indicated by a medical screening. Subjects were instructed to refrain from exercise during the 24-h period before the experimental trials and not to take any supplements such as caffeine. Written informed consent was obtained before study participation, and ethical clearance was obtained from the local ethical committee at the University of Giessen according to the Declaration of Helsinki.
The subjects were tested for their maximal oxygen uptake (V˙O2max) and peak power using a graded exercise test to volitional fatigue on an electromagnetically braked cycle ergometer (ErgoSelect 100, Ergoline, Bitz, Germany). After 5–10 min of warm-up at low intensity, the test started at 50 W, and the power increased by 50 W increments every 3 min until volitional exhaustion. Subjects were required to maintain their cadence at levels higher than 60–80 rpm. HR was recorded continuously during the test using radiotelemetry HR monitor (Polar Electro Öy, Kempele, Finland). Peak power output (PPO) was established as the power output associated with the final completed stage of the test.
At least 1 wk after the preliminary test, participants completed either the HIT or the CONT trial in an alternating raster order. These two trials were separated by a minimum of 7 d. The rate of energy expenditure was calculated by multiplying the power output for each athlete at 90% PPO by the duration of the interval. Each recovery period was calculated by multiplying the power output by the duration of the recovery period. These two values were added together and then multiplied by five to calculate the total amount of work that each athlete completed during the HIT. For calculating total energy expenditure during the CONT, the calorie consumption corresponding to 70% V˙O2max was analyzed and multiplied by 30 min. All exercise protocols started at 0830 h. Upon arrival, a preexercise venous blood sample (30 mL) was collected from an antecubital vein. Subjects proceeded with a 10-min warm-up at a self-selected (low) intensity before each experimental trial.
The CONT exercise protocol consists of a bicycle ergometer test at a constant intensity corresponding to 70% of their V˙O2max for 30 min. The HIT tests consisted of five intervals 3 min each at an intensity of 90% of PPO. Each interval was interrupted by a 3-min active break (cycling without resistance).
At each of the four time points (preexercise, postexercise, 3 h postexercise, and 24 h postexercise), blood samples were collected in vacutainers. Vacutainers contained anticoagulants and were placed on ice, whereas serum sample collected in a serum separation tube was left to clot at room temperature for 15 min. Once the serum sample had clotted, all samples were centrifuged at 4000 rpm for 10 min at 4°C. Serum samples were separated into aliquots and stored in Eppendorf tubes at −80°C until further processing. At all time points, ear prick blood samples were collected and analyzed to measure capillary lactate concentration using a lactate analyzer.
Leukocyte counts and cell isolation
Blood cell counts, hemoglobin, and hematocrit determinations were performed on blood anticoagulated with ethylenediaminetetraacetate using a semiautomated hematology analyzer (F-820; Sysmex, Norderstedt, Germany). Lymphocytes were prepared by density gradient centrifugation. After centrifugation, the lymphocyte band between the sample layer and the Percoll solution was removed. Cell viability was approximately 98%, as demonstrated by Trypan blue exclusion, whereas purity was approximately 95%, as checked by flow cytometry (EPICS XL; Beckman Coulter, Krefeld, Germany) in the forward and sideward scatter mode.
Analysis of T-cell subpopulations, apoptosis, and numbers of progenitor cells
Analysis of T-cell subpopulations were performed by flow cytometry using specific antibodies against CD3, CD4, CD8, CD25, CD28, CD57 (ImmunoTools, Friesoythe, Germany), and CD127 (eBioscience, San Diego, CA). At first, lymphocytes were gated on a forward scatter/side scatter (FS/SS) dot plot and for being CD3 positive. To evaluate differentiation status, additional antibodies were used. Low differentiated T cells were defined as CD3+CD28+CD57−, highly differentiated T cells as CD3+CD28−CD57+, and regulatory T cells (Tregs) as CD4+, CD25+, and CD127−. The detection of apoptosis was performed by using additional labeling with annexin V for each subpopulation. Analyses were performed by flow cytometry (EPICS XL, Beckman Coulter).
The number of progenitor cells was determined by using specific antibodies against CD45, CD34 ((ImmunoTools, Friesoythe, Germany), and KDR (Beckman Coulter, Pasadena, CA). HPC were defined as being positive for CD45 and CD34, whereas endothelial progenitor cells (EPC) were characterized as being negative for CD45 and positive for CD34 and KDR. Absolute cell numbers were calculated by using cell counts and percentage portions from flow cytometric analysis.
Serum and plasma samples for the hormonal analyses were kept frozen at −20°C until assayed. Cortisol concentrations were measured in serum by electrochemiluminescence immunoassay using a Cobas immunoassay system (detection limit, 5.0 nmol·L−1; MVZ, Koblenz, Germany). The concentrations of epinephrine (E) and norepinephrine (NE) in plasma were analyzed by using a commercial ELISA (detection limit for E, 0.01 pg·mL−1; for NE, 0.04 pg·mL−1; DRG Instruments, Marburg, Germany). Thiobarbituric acid–reactive substances (TBARS) are by-products of lipid peroxidation and represent markers of oxidative stress. Concentrations of TBARS in plasma were determined spectrofluometrically. In brief, plasma samples were heated together with thiobarbituric acid reagent at 100°C for 60 min. After cooling on ice, the reaction mixture was neutralized with alkaline methanol. Subsequently, the samples were centrifuged at 3000g and TBARS measured by fluorescence (detection limit, 0.01 nmol·mL−1; excitation wavelength, 532 nm; emission wavelength, 553 nm; Fluorescence Spectrometer LS55, PerkinElmer, Rodgau, Germany) using 1,1,3,3-tetraethoxypropane as a standard. Glucose levels were measured by enzymatic analysis (MVZ). Blood lactate was analyzed using a lactate analyzer (EKF diagnostics, Barleben/Magdeburg, Germany). Free fatty acids (FFA) were analyzed using the ACS/ACOD method and photometric detection (Olympus AU480 Chemistry Analyzer, Center Valley, PA).
Sample size estimation was performed using G Power 3.1. In case of normal distribution, data were analyzed using repeated-measures ANOVAs (mixed model). If this analysis revealed any significant time and time trial interaction effects (P < 0.05), repeated-measures ANOVA was performed. If the result of this test was significant (P < 0.05), Sidak tests were used to compare differences between trials. Differences between preexercise values and values at the postexercise time points were compared with repeated-measures ANOVA. The magnitude of the differences found was assessed through the effect size (ES) Cohen’s d coefficient. If significant main effects were observed, post hoc analysis was conducted using the Bonferroni test. Pearson’s correlation analysis was used to identify any significant relationships. Data are presented as mean ± SD or SEM. In all cases, P < 0.05 was accepted as being significant. Data analysis was performed by SPSS version 22 (IBM® SPSS Statistic 22; IBM GmbH, Munich, Germany).
Exercise protocols were followed by increases of cortisol immediately after CONT (P < 0.0001, F3,75 = 18.78) and HIT (P = 0.0001, F3,77 = 13.10), which were not different between CONT and HIT. Similarly, significant increases of E were found immediately after both exercise protocols (HIT: P = 0.0143, F3,72 = 8.78; CONT: P = 0.012, F3,77 = 11.09) and NE (HIT: P = 0.0043, F3,72 = 12.34; CONT: P = 0.012, F3,77 = 10.33). Although NE values returned to baseline 3 h after the tests, E was still increased 3 h after the HIT exercise (HIT: P = 0.012, F3,72 = 6.50). However, no statistical significant differences between the protocols were found (Table 2).
The total amount of work completed during exercise was not significantly different between the HIT and the CONT trials (HIT = 1570 ± 140 kJ, CONT = 1621 ± 148 kJ). Compared with preexercise values, TBARS increased immediately after both HIT (P = 0.045, F3,84 = 3.84) and CONT (P < 0.0001, F3,84 = 9.34). After the HIT, TBARS decreased back to baseline levels 3 h after exercise, whereas levels were still increased after CONT (P < 0.012, F3,84 = 4.24). However, no significant difference was found between the both exercise protocols. Although no significant changes over time were observed for plasma glucose concentrations, lactate was significantly higher immediately after the HIT compared with CONT (P = 0.032). Three hours after exercise, lactate levels were regulated back to baseline after both tests (Table 3). FFA in plasma increased immediately and 3 h after the CONT exercise (P = 0.001, F3,84 = 7.87), whereas an increase was observed 3 h after the HIT test (P < 0.041, F3,84 = 3.87). The increase of FFA in plasma was significantly higher after the CONT exercise compared with the HIT (P = 0.031) (Table 3).
Mobilized immune cells
After both exercise protocols, a leukocytosis occurred, which persisted up to 3 h after exercise (HIT: P = 0.014, F3,81 = 9.88; CONT: P = 0.011, F3,77 = 12.19). Similarly, absolute numbers of CD3+ (HIT: P = 0.011, F3,81 = 10.18; CONT: P = 0.023, F3,81 = 7.19) (Fig. 1A), CD4+ (HIT: P = 0.012, F3,81 = 10.11; CONT: P = 0.023, F3,81 = 5.19) (Fig. 1B), and CD8+ cells (HIT: P = 0.002, F3,81 = 13.88; CONT: P = 0.012, F3,81 = 8.19) (Fig. 1C) increased immediately after exercise with no significant differences between HIT and CONT.
Regarding low differentiated T cells, an increase in their total cell numbers was found immediately after both exercise tests passing over in a significant decrease below preexercise levels 3 h after the exercise tests (HIT: P = 0.041, F3,77 = 4.71; CONT: P = 0.026, F3,77 = 5.19) (Fig. 1D). By contrast, numbers of highly differentiated T cells were increased at both time points immediately and 3 h after exercise (HIT: P = 0.033, F3,77 = 3.72; CONT: P = 0.029, F3,77 = 5.19). The increase of highly differentiated T cells in blood was significantly higher after HIT compared with CONT (P = 0.0435, ES = 0.63) (Fig. 1E). In addition, the HIT was followed by an increase of Tregs postexercise (P = 0.0331, F3,77 = 4459), whereas no increase of this T-cell subpopulation was observed after the CONT exercise protocol (Fig. 1F).
The percentage of apoptotic CD3+ cells increased significantly 3 h after exercise (HIT: P = 0.043, F3,72 = 4.68; CONT: P = 0.022, F3,74 = 6.12) with no differences between the exercise protocols (Fig. 2A). Similarly, the percentage of annexin positive CD4+ cells (HIT: P = 0.035, F3,72 = 5.78; CONT: P = 0.040, F3,70 = 4.16) and CD8+ cells (HIT: P = 0.023, F3,72 = 5.79; CONT: P = 0.042, F3,70 = 4.22) increased 3 h after exercise (Fig. 2B and C). Here, a difference between the protocols was found at 24 h after exercise (P = 0.011, ES = 0.38) (Fig. 2C). Analyzing the percentage of apoptotic low differentiated T cells revealed that the CONT exercise was followed by a significant higher increase of apoptosis compared with the HIT protocol (P = 0.021, ES = 0.51) (Fig. 2D). The percentage of apoptotic highly differentiated T cells was significantly higher after the HIT compared with CONT immediately after exercise (P < 0.029, ES = 0.57) (Fig. 2E). Regarding Tregs, a significant increase of apoptosis was found 3 h after the CONT exercise (P = 0.011, F3,70 = 6.22), whereas no increase in the percentage of apoptotic Tregs was found after the HIT test (Fig. 2F).
Mechanisms of T-cell mobilization and apoptosis
To analyze the potential mechanism of mobilization or apoptosis of T-cell subpopulations, several correlation analyses were performed. Regarding the mobilization of T cells, a significant association was found between the plasma levels of NE and the percentage of mobilized highly differentiated T cells (r = 0.37, P = 0.049) and Tregs (r = 0.38, P = 0.041) and highly differentiated T cells and E (r = 0.33, P = 0.050). No other correlations were found. Regarding T-cell apoptosis, associations were found between plasma TBARS and low differentiated T cells (r = 0.39, P = 0.041) and TBARS and Tregs (r = 0.58, P = 0.032).
Mobilized progenitor cells
Both HIT and CONT were effective in mobilizing HPC and EPC. Although the HIT was followed by an immediate increase of HPC (P = 0.048, F3,81 = 3.24), the CONT evoked an increase 3 h after exercise (P = 0.024, F3,81 = 3.31). Regarding EPC, both protocols were followed by a slight increase of EPC immediately after exercise (HIT: P = 0.027, F3,75 = 3.205; CONT: P = 0.035, F3,79 = 4.30) without significant differences between the protocols (Fig. 3).
The novel finding of the present investigation is that HIT and CONT exercises affect T-cell subpopulations differently with regard to mobilization and apoptosis. Although CONT exercise induced a higher increase of apoptosis in low differentiated T cells, both the mobilization and the apoptosis of highly differentiated T cells were higher after the HIT exercise. Furthermore, HIT induced a mobilization of regulatory T cells, whereas CONT induced apoptosis in Tregs. By contrast, the mobilization of progenitor cells did not differ between both exercise protocols.
Most physiological responses observed after the HIT test were similar to continuous intensive endurance and strength exercise protocols (25). After HIT, we found an increase of sympathetic activation indicated by an increase of plasma E, NE, and cortisol; increased oxidative stress indicated by an increase of TBARS; and an enhanced energy turnover indicated by an increase of blood lactate and FFA. All these parameters were similarly regulated after HIT and CONT except for lactate and FFA. Lactate levels in blood were higher after the HIT, indicating a stronger anaerobic stimulus, whereas the increased FFA levels after CONT indicate a more aerobic stimulus and an increased use of fatty acids (25).
The rise of these hormones and metabolites in plasma suggests that T-cell numbers and functions are affected. Given a differentiated response of T-cell subsets to external signals, T cells were subdivided in our study with respect to subpopulations and differentiation stage (20). Regarding the mobilization of lymphocytes, an increase of total T cells, T helper cells, and cytotoxic T cells was found with no differences between the exercise protocols. In line with previous studies, the mobilization of CD8+ cells was relatively higher compared with CD4+ cells after exercise (21). The increase of highly differentiated T cells in the circulation was higher compared with low differentiated T cells. Thereby, the absolute number of mobilized highly differentiated cells was significantly higher after HIT compared with CONT. The amplified mobilization of these cells is in line with previous studies (5,31) and is suggested to be driven by the higher intensities (30,38). The physiological reason for the exercise-induced increase of highly differentiated T cells is still unknown. It is suggested that these cells are more frequently residing at the vessel wall and in secondary lymphoid organs (11,12). These compartments might contribute to lymphocytosis by changing their adhesive interactions with lymphocytes in response to catecholamines (4,9). It is supposed that HIT induces a stronger mobilization of highly differentiated cells because of its repeated sympathetic stimulation, an assumption that is supported by the longer-lasting increase of plasma E after exercise. However, besides catecholamines, we cannot exclude that cortisol is also involved in changes of lymphocyte numbers because corticosteroid treatment is also known to affect lymphocyte redistribution (12,15).
Regarding cell death, previous studies observed an increase of apoptotic lymphocytes after intensive bouts of exercise (13,19). Thereby, exercise intensity is assumed to be a main effector of apoptotic processes (20). In line with these observations, we found that both exercise protocols were followed by an increase of apoptotic CD3+, CD4+, and CD8+ lymphocytes. These findings are similar to previous studies demonstrating that both interval exercise and CONT exercise induced apoptosis in total T cells, T helper cells, and cytotoxic T cells (21). The reasons for the different responses of low or highly differentiated cells after the exercise protocols seem to be related to their mobilization pattern. In general, it is known that CD28− T cells undergo less apoptosis than their CD28+ counterparts (24). One cause of exercise-induced apoptosis is activation-induced cell death, eradicating activated T cells by the generation of death signals after Fas–FasL interaction, leading to the phosphorylation of the Fas receptor death domain and finally to apoptosis by the activation of several caspases (15). The inhibitor of this pathway, the Fas-associated death domain-like IL-1-converting enzyme inhibitory protein, is increased in CD4+CD28− T cells and interacts either with caspases 8 and 10 or with the Fas-associated death domain followed by an inhibition of cell death by interrupting Fas signaling (36). Regarding other apoptotic pathways, highly differentiated cells are also less sensitive by the exhibition of an increased level of antiapoptotic Bcl-2 (29). Therefore, it is assumed that not the susceptibility to apoptosis but the high number of mobilized highly differentiated cells is the main reason for the increased rate of apoptosis after exercise. In particular, circulating cells are more likely to get in contact with potential mediators of apoptosis in plasma, such as ROS or cortisol. Similar reasons might account for the increased percentage of apoptosis in low differentiated T cells after CONT. After CONT, low differentiated T cells are mobilized and exposed to a higher amount of ROS indicated by the increased generation of TBARS. ROS have previously been identified to be a stimulus for cell death during exercise (10). In particular, low differentiated T cells are known to be susceptible to apoptosis induced by oxidative stress (36). The relevance of these processes for the immune competence is speculative. Given the deletion of mainly low differentiated T cells after the CONT, there might be a temporary loss of immune cells, which is relevant against new invading pathogens. Otherwise, after the HIT, an increased deletion of highly differentiated cells might affect the risk for the reactivation of latent virus infections (2,12,36). The increased deletion of highly differentiated T cells might also be a reason for the capability of habitual exercise for delaying the onset of immunosenescence. In this regard, exercise might create a “vacant space” for newly functional T cells to expand the naive T-cell repertoire (30). A limitation of current study is that we did not evaluate differences in low or high differentiated CD4 and CD8 cells (17,23,38). In addition, a further limitation is that we did not analyze cytomegalovirus (CMV) serostatus. The mobilization of T cells with a highly differentiated phenotype to exercise is higher in people with a latent CMV infection (33). Given that subjects with high numbers of mobilized cells also have the highest portion of apoptosis, cell death in subject positive for CMV might have highest rate of lymphocyte apoptosis.
Tregs are suppressive subsets of CD4+ T cells that function to antagonize inflammatory responses. The most specific marker of Tregs represents the marker FoxP3. Because of its intracellular nature, we use the surrogate extracellular marker CD127 whose expression is reported to have an inverse relationship with FoxP3 (8,16,34). Interestingly, HIT and CONT differently affect both mobilization and apoptosis of Tregs. Although the HIT exercise mainly stimulates Tregs mobilization, CONT was followed by increased apoptosis. In general, the number of peripheral Treg cells is a crucial determinant of the regulatory burden on the immune system. Having too few of these cells can trigger fatal autoimmune responses, whereas having too many can cause immune suppression (15). Accordingly, it can be speculated that the increased number of Tregs after HIT indicates an increased anti-inflammatory effect of this type of exercise. However, if the increase of Tregs after HIT has any clinical relevance, such as inducing a period of immunosuppression, remains speculative (26). The increased mobilization of Tregs after HIT suggests that these cells were sensitive for more intensive bouts of exercise. Recently, it was shown that Tregs also express functional B2AR. After the activation of these receptors, intracellular cAMP levels increase, leading to a protein kinase A (PKA)–dependent CREB phosphorylation. This is suggested to increase the suppressive activity of Tregs (7). Accordingly, the repeated sympathetic stimuli during the HIT might mobilize and activate Tregs more sufficiently compared with CONT followed by an increased inflammatory regulative action after the HIT. Possibly, these mechanisms might also affect the delay of immunosenescence in physically active individuals (27,32). The increased rate of apoptotic Tregs after the CONT exercise might also be related to the increased ROS production, which is known to be an important apoptosis inducer in Tregs (38). Commonly, increased Tregs apoptosis, which was observed after the CONT, might indicate an more increased pro-inflammatory reaction after exercise (13,35). However, the changes in the percentage of apoptosis are only marginal. In this regard, Tregs are known to have a high basal proliferation rate compared with conventional T cells (7,38). Therefore, the unusually high turnover of circulating Treg cell population allows a rapid response to homeostatic perturbations (19,35). Accordingly, it can be speculated that the body quickly compensates these minor variations in Treg numbers after different exercise protocols without any clinical differences (19).
Both acute and chronic exercise training mobilize HPC and EPC into the peripheral blood (1,14). It has been proposed that these cells are involved in regeneration and adaptation processes such as tissue repair, myofiber formation, hematopoiesis, and endothelial regeneration (1). In this study, we found that both exercise regimens were able to increase numbers of HPC as well as EPC in blood with no differences between the protocols. Therefore, it is assumed that both exercise types exhibit a similar potential for regeneration and adaptation. Recently, we demonstrated that the mobilization of progenitor cells seem to be connected with signals induced by apoptotic cells (19). Given the differentiated apoptosis response of T-cell subpopulations after the exercise, it is suggested that apoptosis signals for progenitor cell mobilization have no subset specificity.
Taken together, this study demonstrated that HIT and CONT exercise tests induce a subset-specific pattern of T-cell mobilization and apoptosis. HIT mobilized more efficiently low differentiated T cells and Tregs, whereas apoptosis is induced in highly differentiated T cells. These processes are speculated to temporary impair immunity against persistent infections, whereas immunity against new pathogens is not negatively affected. By contrast, CONT deletes mainly low differentiated T cells and Tregs, which might temporary affect defense against new infectious agents and control of inflammatory responses. Hence, these experimental findings indicate that HIT exercise does not more critically affect immunity, despite its intensity, compared with CONT exercise. However, any clinical relevance of these T-cell changes has to be elucidated in future studies.
There is no conflict of interest. There is no funding source. Results of the present study do not constitute endorsement by the American College of Sports Medicine.
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