High intensity interval exercise increases the frequency of peripheral PD-1+ CD8+ central memory T-cells and soluble PD-L1 in humans

Alex Wadley, Tom Cullen, Jordan Vautrinot, Gary Keane, Nicolette Bishop, Steven Coles

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    15 Citations (Scopus)
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    Exercise can exert anti-inflammatory effects in an intensity-dependent manner; however, the mechanisms mediating these effects are continually being established. Programme Death Receptor-1 (PD-1) is a membrane bound receptor that maintains immune tolerance by dampening immune cell interactions, such as those mediated by cytotoxic T-cell lymphocytes (CD8 +). The aim of this study was to characterise sub-populations of CD8 + T-cells with regards to their expression of PD-1 before and immediately after exercise. Interleukin (IL)-6, soluble PD-1 (sPD-1) and its ligand (sPD-L1) were also quantified in plasma. Eight individuals (mean ​± ​SD: age 29 ​± ​5 years; BMI 24.2 ​± ​3.4 ​kg ​m 2; V˙O 2max 44.5 ​± ​6.4 ​ml ​kg −1·min −1) undertook two time and energy-matched cycling bouts in a counterbalanced study design: one of moderate intensity (MOD) and a bout of high intensity interval exercise (HIIE). Both MOD and HIIE increased the number, but not the proportion of circulating CD8 + PD-1+ cells, with no differences between trials. Within the CD8 + PD-1+ pool, the expression of PD-1 increased on central memory cells following HIIE only (fold change: MOD 1.0 vs HIIE +1.4), as well the concentration of CD8+PD-1+ memory cells within the circulation (cells/uL: MOD -0.4 vs HIIE +5.8). This response composed a very small part of the exercise-induced CD8 + lymphocytosis (Pre-Ex: 0.38% to Post-Ex: 0.69%; p ​> ​0.05). sPD-L1 and IL-6 concentration increased in tandem following MOD and HIIE (r ​= ​0.57; P ​= ​0.021), with a reciprocal decline in sPD-1 observed. The current data demonstrate that PD-1+ CD8 + lymphocytes were mobilised following both MOD and HIIE. Both the number of central memory CD8 + T-cells expressing PD-1 and the expression level on these cells were increased following HIIE only. This intensity-dependent phenotypic response, in conjunction with increased circulatory sPD-L1 may represent an aspect of the anti-inflammatory response to exercise and warrants further investigation.

    Original languageEnglish
    Article number100049
    Number of pages7
    JournalBrain Behavior and Immunity - Health
    Early online date14 Feb 2020
    Publication statusPublished - Mar 2020

    Bibliographical note

    ©2020 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).


    • Exercise
    • Immune checkpoints
    • Immune tolerance
    • sPD-1
    • sPD-L1

    ASJC Scopus subject areas

    • Nephrology


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