Influence of Exercise on Exhausted and Senescent T Cells: A Systematic Review

Donovan, Thomasina; Bain, Amanda L.; Tu, Wenjuan; Pyne, David B.; Rao, Sudha

doi:10.3389/fphys.2021.668327

Cited by 11 publications

(8 citation statements)

References 66 publications

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“…While conventional T cell mobilization appears to be unimpaired after acute exercise, alterations in CD57 and perforin may have functional implications. We report an increase in CD8 + CD57 + counts post-exercise, which is consistent with previous work in healthy men ( 42 ) as acute exercise generally increases mobilization of senescent (CD28 − CD57 + ) T cells ( 43 ). In contrast, the frequency of CD8 + CD57 + cells was unchanged, with a non-significant 6.6% decrease at 0H.…”

Section: Discussionsupporting

confidence: 92%

Acute exercise induces distinct quantitative and phenotypical T cell profiles in men with prostate cancer

Hanson

Sakkal

Bates

et al. 2023

Front. Sports Act. Living

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BackgroundReduced testosterone levels can influence immune system function, particularly T cells. Exercise during cancer reduces treatment-related side effects and provide a stimulus to mobilize and redistribute immune cells. However, it is unclear how conventional and unconventional T cells (UTC) respond to acute exercise in prostate cancer survivors compared to healthy controls.MethodsAge-matched prostate cancer survivors on androgen deprivation therapy (ADT) and those without ADT (PCa) along with non-cancer controls (CON) completed ∼45 min of intermittent cycling with 3 min at 60% of peak power interspersed by 1.5 min of rest. Fresh, unstimulated immune cell populations and intracellular perforin were assessed before (baseline), immediately following (0 h), 2 h, and 24 h post-exercise.ResultsAt 0 h, conventional T cell counts increased by 45%–64% with no differences between groups. T cell frequency decreased by −3.5% for CD3+ and −4.5% for CD4+ cells relative to base at 0 h with CD8+ cells experiencing a delayed decrease of −4.5% at 2 h with no group differences. Compared to CON, the frequency of CD8+CD57+ cells was −18.1% lower in ADT. Despite a potential decrease in maturity, ADT increased CD8+perforin+ GMFI. CD3+Vα7.2+CD161+ counts, but not frequencies, increased by 69% post-exercise while CD3+CD56+ cell counts increased by 127% and were preferentially mobilized (+1.7%) immediately following the acute cycling bout. There were no UTC group differences. Cell counts and frequencies returned to baseline by 24 h.ConclusionFollowing acute exercise, prostate cancer survivors demonstrate normal T cell and UTC responses that were comparable to CON. Independent of exercise, ADT is associated with lower CD8+ cell maturity (CD57) and perforin frequency that suggests a less mature phenotype. However, higher perforin GMFI may attenuate these changes, with the functional implications of this yet to be determined.

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Section: Discussionsupporting

confidence: 92%

Acute exercise induces distinct quantitative and phenotypical T cell profiles in men with prostate cancer

Hanson

Sakkal

Bates

et al. 2023

Front. Sports Act. Living

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“… 102 A systematic review of studies including RCT demonstrated a beneficial effect of repeated aerobic exercise or endurance resistance training on CD28 expression of CD8 + T cells irrespective of age or level of sedentarism. 103 This occurred despite a temporary increase in senescent CD8 + CD28 null T cells immediately postexercise. 103 Cardioprotective drugs such as lipid‐lowering statins have pleiotropic effects, which include a lowering of circulating CD4 + CD28 null T cells.…”

Section: Introductionmentioning

confidence: 99%

“… 103 This occurred despite a temporary increase in senescent CD8 + CD28 null T cells immediately postexercise. 103 Cardioprotective drugs such as lipid‐lowering statins have pleiotropic effects, which include a lowering of circulating CD4 + CD28 null T cells. 6 , 29 This is likely related to anti‐inflammatory properties and pro‐apoptotic effects on senescent T cells.…”

Section: Introductionmentioning

confidence: 99%

Immunosenescence: an unexplored role in glomerulonephritis

2022

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Immunosenescence is a natural ageing phenomenon with alterations in innate and especially adaptive immunity and contributes to reduced antimicrobial defence and chronic low‐grade inflammation. This is mostly reflected by an increase in organ‐directed and/or circulating reactive and cytolytic terminally differentiated T cells that have lost their expression of the costimulatory receptor CD28. Apart from being induced by a genetic predisposition, ageing or viral infections (particularly cytomegalovirus infection), immunosenescence is accelerated in many inflammatory diseases and uraemia. This translates into an enhancement of vascular inflammation and cardiovascular disease varying from endothelial dysfunction to plaque rupture. Emerging data point to a mechanistic role of CD28null T cells in glomerulonephritis, where they initiate and propagate local inflammation in concordance with dendritic cells and macrophages. They are suitably equipped to escape immunological dampening by the absence of homing to lymph nodes, anti‐apoptotic properties and resistance to suppression by regulatory T cells. Early accumulation of senescent CD28null T cells precedes glomerular or vascular injury, and targeting these cells could open avenues for early treatment interventions that aim at abrogating a detrimental vicious cycle.

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“…Similarly, Turner et al ( 12 ) demonstrated a greater increase in late differentiated CD27-CD28- CD8+ T-cells following 60 min of vigorous running exercise than less differentiated cells. CD28-CD57+ T-cells are also significantly mobilized by exercise ( 13 ). This selective mobilization of later differentiated T-cells is due to the greater expression of type 2 beta-adrenergic receptors by highly differentiated T-cells, as epinephrine binding to these receptors promotes cell extravasation into the bloodstream ( 11 , 15 ).…”

Section: Introductionmentioning

confidence: 99%

“…While TM T-cells are prevalent in healthy human subjects and are functionally distinct from CM and EM ( 3 ), their response to exercise has not been reported. Given the enhanced effector properties of TM relative to CM, the enhanced proliferative capacity of TM relative to EM, and the fact that TM T-cells comprise a substantial portion of the T-cells present in the blood ( 5 ), describing the mobilization of these cells by acute exercise is important to fully understanding the changes in T-cells that occur with exercise Further, while CD28-CD57+ T-cells are known to be mobilized by exercise ( 13 ), their relative mobilization compared to later differentiated subsets (EM, EMRA) lacking CD57 is not yet known. Finally, to our knowledge, there are no reports of the mobilization of CD28 + CD57+ T-cells with exercise.…”

Section: Introductionmentioning

confidence: 99%

Characterization of transitional memory CD4+ and CD8+ T-cell mobilization during and after an acute bout of exercise

Hunt

Elzayat

Markofski

et al. 2023

Front. Sports Act. Living

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T-cell subsets, including naïve (NA), central memory (CM), transitional memory (TM), effector memory (EM), and RA + effector memory (EMRA), differ in phenotype and function. T-cells are mobilized by exercise, with differences in the magnitude of mobilization between subsets. However, the response of TM T-cells to exercise has not yet been described. Further, T-cells expressing the late differentiation marker CD57 are known to be highly responsive to exercise, but the relative response of CD57 + and CD57- within T-cell subsets is unknown. We therefore aimed to characterize the exercise-induced mobilization of TM T-cells, as well as to compare the exercise response of CD57 + and CD57- cells within T-cell subsets.MethodsSeventeen participants (7 female; aged 18–40 years) cycled 30 min at 80% of their estimated maximum heart rate. Venous blood obtained pre, post, and 1H post-exercise was analyzed by flow cytometry. CD45RA, CCR7, and CD28 expression within CD4 + and CD8+ T-cells identified NA, CM, TM, EM, and EMRA subsets. CD57 expression within EM, EMRA, and CD28+ T-cells was also quantified. The relative mobilization of each subset was compared by calculating fold change in cell concentration during (ingress, post/pre) and after exercise (egress,1H post/post). Cytomegalovirus (CMV) serostatus was determined by ELISA and was considered in models.ResultsTM CD8+ T-cell concentration was greater post-exercise than pre-exercise (138.59 ± 56.42 cells/µl vs. 98.51 ± 39.68 cells/µl, p < 0.05), and the proportion of CD8 + with a TM phenotype was elevated 1H post-exercise (1H: 32.44 ± 10.38% vs. Pre: 30.15 ± 8.77%, p < 0.05). The relative mobilization during and after exercise of TM T-cells did not differ from NA and CM but was less than EM and EMRA subsets. Similar results were observed within CD4+ T-cells. CD57 + subsets of CD28+ T-cells and of EM and EMRA CD8+ T-cells exhibited a greater relative mobilization than CD57- subsets (all p < 0.05).ConclusionThese results indicate TM CD4 + and CD8+ T-cells are transiently mobilized into the blood with exercise, but not to as great of an extent as later differentiated EM and EMRA T-cells. Results also indicate CD57 identifies highly exercise responsive cells within CD8+ T-cell subsets.

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Influence of Exercise on Exhausted and Senescent T Cells: A Systematic Review

Cited by 11 publications

References 66 publications

Acute exercise induces distinct quantitative and phenotypical T cell profiles in men with prostate cancer

Acute exercise induces distinct quantitative and phenotypical T cell profiles in men with prostate cancer

Immunosenescence: an unexplored role in glomerulonephritis

Characterization of transitional memory CD4+ and CD8+ T-cell mobilization during and after an acute bout of exercise

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