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Physical exercise modulates the homeostasis of human regulatory T cells  Max Weinhold, MA, Alexander Shimabukuro-Vornhagen, MD, Axel Franke, MD, Sebastian.

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Presentation on theme: "Physical exercise modulates the homeostasis of human regulatory T cells  Max Weinhold, MA, Alexander Shimabukuro-Vornhagen, MD, Axel Franke, MD, Sebastian."— Presentation transcript:

1 Physical exercise modulates the homeostasis of human regulatory T cells 
Max Weinhold, MA, Alexander Shimabukuro-Vornhagen, MD, Axel Franke, MD, Sebastian Theurich, MD, Patrick Wahl, PhD, Michael Hallek, MD, Annette Schmidt, PhD, Timo Schinköthe, PhD, Joachim Mester, PhD, Michael von Bergwelt-Baildon, MD, PhD, Wilhelm Bloch, MD  Journal of Allergy and Clinical Immunology  Volume 137, Issue 5, Pages e8 (May 2016) DOI: /j.jaci Copyright © Terms and Conditions

2 Fig 1 Correlation of PA with Treg-cell frequencies. A, Disciplines ranked according to median relVo2peak values. B, Treg-cell frequencies of athletes (n = 245) and healthy controls (n = 35). C, Comparison of sexes demonstrated that female athletes (n = 62) had significantly lower Treg-cell frequencies than did relVo2peak-matched male athletes (n = 62). D, The percentage of Treg cells differed significantly across the 3 groups. Female (E) and male (F) athletes demonstrated a similar relVo2peak dependence of the percentage of circulating Treg cells. In Fig 1, A, the whiskers indicate the minimum and maximum values. Journal of Allergy and Clinical Immunology  , e8DOI: ( /j.jaci ) Copyright © Terms and Conditions

3 Fig 2 Exercise-induced increase in Treg cells. To validate the association of physical exercise with the frequency of Treg cells, we analyzed blood samples of 19 members of the German National Hockey Team before and after their training. The time-dense, high-intensity training program resulted in a significant increase in the frequency of circulating Treg cells from 7.21% to 8.14%. Journal of Allergy and Clinical Immunology  , e8DOI: ( /j.jaci ) Copyright © Terms and Conditions

4 Fig E1 Intensity of PA correlates with Treg-cell frequency. Linear regression analysis revealed a statistically significant correlation between the average relVo2peak values for the disciplines correlated and mean frequency of Treg cells in the peripheral blood of athletes (r2 = 0.26; P = .02). Each dot represents 1 sport discipline. Journal of Allergy and Clinical Immunology  , e8DOI: ( /j.jaci ) Copyright © Terms and Conditions

5 Fig E2 Absolute Treg-cell counts increase with relVo2peak. Shown are boxplots of the absolute numbers of CD3+ CD4+ CD25high CD127low Treg cells. The results are grouped by relVo2peak values. The data are displayed as box-and-whisker plots. The whiskers indicate 1.5 interquartile range. One-way ANOVA was used to test for differences followed by Tukey post hoc comparisons. Journal of Allergy and Clinical Immunology  , e8DOI: ( /j.jaci ) Copyright © Terms and Conditions

6 Fig E3 CD3+ CD4+ CD25high CD127low Treg cells suppress T-cell proliferation. A, To confirm that the CD3+ CD4+ CD25high CD127low T-cell subset expresses FOXP3, we performed flow cytometric analysis of peripheral blood of 8 athletes. Shown is a representative fluorescence-activated cell sorter plot. B, The boxplot shows that on average 90.2% ± 5.5% of CD3+CD4+CD127lowCD25high Treg cells expresses FOXP3. C, To assess the immunoregulatory function of the CD3+CD4+CD127lowCD25high T-cell subset, we performed an inhibition assay. Purified CD3+CD4+CD127+CD25− T cells were stimulated using magnetic beads coated with anti-CD3 and anti-CD28 antibodies. Addition of FACS-purified CD3+ CD4+ CD25high CD127low Treg cells resulted in a significant inhibition of proliferation of CD3+CD4+CD127+CD25− T cells (adjusted P = .0211). Shown are the results of 2 independent experiments (n = 4). The results are presented as proliferation relative to CFSE-labeled CD3+CD4+CD127+CD25− T cells, which were stimulated with beads in the absence of Treg cells. CFSE-labeled CD3+CD4+CD127+CD25− T cells, which were not stimulated with beads, were used as controls. Bar charts represent the means ± SD. D, Results of depletion assays confirmed the inhibitory function of Treg cells. In addition, there was a significant difference (P = .04, Student t test) in the inhibitory effect of Treg-cell depletion between elite athletes (n = 30) and sex- and age-matched healthy controls (n = 30). Shown is the proliferation index (proliferation after Treg-cell depletion/proliferation without Treg-cell depletion). Bar charts represent the means ± SD. *P < .05. Journal of Allergy and Clinical Immunology  , e8DOI: ( /j.jaci ) Copyright © Terms and Conditions

7 Fig E4 Exercise affects serum levels of TGF-β. The serum levels of the proinflammatory cytokines IL-1β, IL-6, and TNF-α as well as the anti-inflammatory cytokines IL-10 and TGF-β were measured in the serum of athletes with low (n = 14) and high (n = 15) relVo2peak values using ELISA. The data are displayed as box-and-whisker plots. The whiskers indicate 1.5 interquartile range. Journal of Allergy and Clinical Immunology  , e8DOI: ( /j.jaci ) Copyright © Terms and Conditions

8 Fig E5 Neutralization of TGF-β increases T-cell proliferation. Purified CD4+ T cells were stimulated with magnetic beads coated with anti-CD3 and anti-CD28 antibodies. Addition of neutralizing anti–TGF-β antibodies resulted in a significant increase in CD4+ T-cell proliferation compared with controls, demonstrating that TGF-β exerts a suppressive effect (P = .001; Student t test). Bar charts represent the means of the relative proliferation ± SD (n = 8). Mean proliferation of control CD4+ T cells was defined as 100%. Journal of Allergy and Clinical Immunology  , e8DOI: ( /j.jaci ) Copyright © Terms and Conditions

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