Does exercise attenuate age- and disease-associated dysfunction in unconventional T cells? Shining a light on overlooked cells in exercise immunology

Hanson, Erik D.; Bates, Lauren; Bartlett, David B.; Campbell, John P.

doi:10.1007/s00421-021-04679-4

Cited by 8 publications

(11 citation statements)

References 197 publications

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“…An increasing body of literature has established the effects of aging on the function of conventional T cells and their phenotype [ 20 ], yet little is known on the exercise effects on ILCs. Similar to unconventional T cells (i.e., MAIT, NKT, and γδ T cells), ILCs can be easily found near the barrier sites such as the skin, lung, and mucosal tissues, rather than in circulation, playing an important role in cancer, asthma, and inflammatory bowel disease [ 50 ]. Here, we show for the first time that although these cells can be mobilized in the peripheral blood compartment, their exercise responsiveness depends on CMV infection history.…”

Section: Discussionmentioning

confidence: 99%

Cytomegalovirus Infection Impairs the Mobilization of Tissue-Resident Innate Lymphoid Cells into the Peripheral Blood Compartment in Response to Acute Exercise

Cho

Theall

Stampley

et al. 2021

Viruses

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Circulating immune cell numbers and phenotypes are impacted by high-intensity acute bouts of exercise and infection history with the latent herpesviruses cytomegalovirus (CMV). In particular, CMV infection history impairs the exercise-induced mobilization of cytotoxic innate lymphoid cells 1 (ILC1) cells, also known as NK cells, in the blood. However, it remains unknown whether exercise and CMV infection modulate the mobilization of traditionally tissue-resident non-cytotoxic ILCs into the peripheral blood compartment. To address this question, 22 healthy individuals with or without CMV (20–35 years—45% CMVpos) completed 30 min of cycling at 70% VO2 max, and detailed phenotypic analysis of circulating ILCs was performed at rest and immediately post-exercise. We show for the first time that a bout of high-intensity exercise is associated with an influx of ILCs that are traditionally regarded as tissue-resident. In addition, this is the first study to highlight that latent CMV infection blunts the exercise-response of total ILCs and progenitor ILCs (ILCPs). These promising data suggest that acute exercise facilitates the circulation of certain ILC subsets, further advocating for the improvements in health seen with exercise by enhancing cellular mobilization and immunosurveillance, while also highlighting the indirect deleterious effects of CMV infection in healthy adults.

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Section: Discussionmentioning

confidence: 99%

Cytomegalovirus Infection Impairs the Mobilization of Tissue-Resident Innate Lymphoid Cells into the Peripheral Blood Compartment in Response to Acute Exercise

Cho

Theall

Stampley

et al. 2021

Viruses

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“…In OW post-menopausal women 12 weeks of exercise training may elicit a partial restoration of the MAIT-cell response; however, more research is needed to elucidate age and obesity-related deficits. Currently, the literature examining unconventional T-cell response to exercise [7], and especially MAIT-cell response, is quite limited. To date, only acute aerobic exercise in healthy young men [16,17] and acute and chronic exercise in breast cancer survivors [19] have been published.…”

Section: Discussionmentioning

confidence: 99%

“…Cells were phenotyped using immunofluorescence labeling of cell surfaces with mouse anti-human monoclonal antibodies prior to stimulation, as previously described [7]. PBMCs were also stimulated with 2 ng/mL phorbol 12-myristate 13-acetate (PMA) and 1 ng/mL ionomycin or vehicle controls for 4 h at 37 • C and 5% CO 2 to induce intracellular cytokine production [7] that was stained using mouse anti-human monoclonal antibodies in fixation and permeabilization buffer (BD Biosciences, Franklin Lakes, NC, USA). Cells were washed to remove excess antibody and suspended in 300 µL of cell staining buffer for flow cytometry analysis.…”

Section: Blood Analysismentioning

confidence: 99%

“…One type of unconventional T-cell that possesses qualities of innate and adaptive immunity are mucosal-associated invariant T (MAIT) cells. MAIT-cells are identified by the expression of a semi-invariant T-cell receptor (TCR) Vα7.2 and CD161 [7]. Following activation, MAIT-cells have the ability to rapidly produce Th17 cytokines (e.g., IL-17, TNF-α, IFN-γ) while also possessing cytotoxic function [7].…”

Section: Introductionmentioning

confidence: 99%

“…MAIT-cells are identified by the expression of a semi-invariant T-cell receptor (TCR) Vα7.2 and CD161 [7]. Following activation, MAIT-cells have the ability to rapidly produce Th17 cytokines (e.g., IL-17, TNF-α, IFN-γ) while also possessing cytotoxic function [7]. MAIT-cells are reportedly altered in obese populations including lower MAIT-cell counts/frequencies in peripheral blood [8][9][10][11][12], and differing cytokine production (compared to healthy controls) including a reduced (or even lost) ability to produce IFN-γ [13] and an elevated IL-17 production [11].…”

Section: Introductionmentioning

confidence: 99%

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Mucosal-Associated Invariant T Cell Response to Acute Exercise and Exercise Training in Older Obese Women

Bates

Hanson

Levitt

et al. 2021

Sports

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(1) Background: Obesity is a major global public health concern as it is associated with many of the leading causes of preventable deaths. Exercise reduces obesity-induced inflammation; however, it is unknown how exercise training may impact mucosal associated invariant T (MAIT) cells in overweight/obese (OW) post-menopausal women. Therefore, the purpose of this study was to investigate (i) circulating MAIT-cells at rest in OW vs. Lean women, (ii) the response of MAIT-cells to a single bout of combined aerobic and resistance exercise, and (iii) the effects of 12 weeks of exercise training (EX) or educational program (ED) on the MAIT-cell response in OW. (2) Methods: OW completed an acute exercise session or sitting control, underwent 12 weeks of exercise training or received educational materials, and then repeated the exercise session/sitting control. Lean post-menopausal women provided a baseline comparison. (3) Results: OW had lower circulating MAIT-cells at rest than Lean prior to exercise training; however, after training EX displayed improved MAIT-cell frequency. Additionally, prior to training EX did not exhibit MAIT-cell mobilization/egress, however, both improved after training. (4) Conclusions: Reduced MAIT-cell frequency and ability to mobilize/egress were potentially partially rescued in EX after 12 weeks of exercise training; however, further research is needed to elucidate age or obesity-induced attenuations in MAIT-cells.

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Age-dependent frequency of unconventional T cells in a healthy adult Caucasian population: a combinational study of invariant natural killer T cells, γδ T cells, and mucosa-associated invariant T cells

et al. 2022

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Unconventional T cells show distinct and unique features during antigen recognition as well as other immune responses. Their decrease in frequency is associated with various autoimmune disorders, allergy, inflammation, and cancer. The landscape frequency of the unconventional T cells altogether (iNKT, γδ T, and MAIT) is largely unestablished leading to various challenges affecting diagnosis and research in this field. In this study, we have established the age group–wise frequency of iNKT, γδ T, and MAIT cells altogether on a total of 203 healthy adult samples of the Caucasian population. The results revealed that iNKT cells were 0.095%, γδ T cells were 2.175%, and MAIT cells were 2.99% of the total T cell population. γδ and MAIT cell frequency is higher in younger age groups than elderly; however, there is no statistically significant difference in the frequency of iNKT cells. Furthermore, γδ and MAIT cells were negatively correlating with age, supporting immunosenescence, unlike iNKT cells. Our finding could be used for further age-wise investigation of various pathological conditions such as cancer and their prognosis, autoimmune diseases and their pathogenicity.

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Does exercise attenuate age- and disease-associated dysfunction in unconventional T cells? Shining a light on overlooked cells in exercise immunology

Cited by 8 publications

References 197 publications

Cytomegalovirus Infection Impairs the Mobilization of Tissue-Resident Innate Lymphoid Cells into the Peripheral Blood Compartment in Response to Acute Exercise

Cytomegalovirus Infection Impairs the Mobilization of Tissue-Resident Innate Lymphoid Cells into the Peripheral Blood Compartment in Response to Acute Exercise

Mucosal-Associated Invariant T Cell Response to Acute Exercise and Exercise Training in Older Obese Women

Age-dependent frequency of unconventional T cells in a healthy adult Caucasian population: a combinational study of invariant natural killer T cells, γδ T cells, and mucosa-associated invariant T cells

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