Pre-existing hypertension dominates γδT cell reduction in human ischemic stroke.

Mateusz G Adamski,Helen Durkin,Yan Li,Hua Yu,Steven A Soper,Michael Murphy,Qing Hao,Alison E Baird,Chloe Seales-Bailey,Erin Wagner,Jason R Lees

doi:10.1371/journal.pone.0097755

Mateusz G Adamski, Helen Durkin + Show 9 more

Open Access

https://doi.org/10.1371/journal.pone.0097755

Copy DOI

Abstract

T lymphocytes may play an important role in the evolution of ischemic stroke. Depletion of γδT cells has been found to abrogate ischemia reperfusion injury in murine stroke. However, the role of γδT cells in human ischemic stroke is unknown. We aimed to determine γδT cell counts and γδT cell interleukin 17A (IL-17A) production in the clinical setting of ischemic stroke. We also aimed to determine the associations of γδT cell counts with ischemic lesion volume, measures of clinical severity and with major stroke risk factors. Peripheral blood samples from 43 acute ischemic stroke patients and 26 control subjects matched on race and gender were used for flow cytometry and complete blood count analyses. Subsequently, cytokine levels and gene expression were measured in γδT cells. The number of circulating γδT cells was decreased by almost 50% (p = 0.005) in the stroke patients. γδT cell counts did not correlate with lesion volume on magnetic resonance diffusion-weighted imaging or with clinical severity in the stroke patients, but γδT cells showed elevated levels of IL-17A (p = 0.048). Decreased γδT cell counts were also associated with older age (p = 0.004), pre-existing hypertension (p = 0.0005) and prevalent coronary artery disease (p = 0.03), with pre-existing hypertension being the most significant predictor of γδT cell counts in a multivariable analysis. γδT cells in human ischemic stroke are reduced in number and show elevated levels of IL-17A. A major reduction in γδT lymphocytes also occurs in hypertension and may contribute to the development of hypertension-mediated stroke and vascular disease.

Highlights

Stroke is a leading cause of death and disability in the United States [1]
After ischemia reperfusion injury, increased macrophage IL-23 secretion commenced after day 1 and increased cdT cell IL-17 secretion commenced after day 3
Intracellular cytokine staining confirmed that cdT cells were the main source of IL-17, CD4+ and cdTCR- T cells were the main sources of INF-c

Summary

Introduction

CdT cells are a population of T lymphocytes that comprise between 0 and 7% of circulating CD3+ cells [8]. These cells express cd T cell receptors (TCR), whereas the majority of T lymphocytes express abTCR. After ischemia reperfusion injury, increased macrophage IL-23 secretion commenced after day 1 and increased cdT cell IL-17 secretion commenced after day 3. In this same model, infarct size was reduced on day 1 in IL-23 knockout (KO) mice and on day 4 in IL-17 KO mice but was not altered in INF-c KO mice. Intracellular cytokine staining confirmed that cdT cells were the main source of IL-17, CD4+ and cdTCR- T cells were the main sources of INF-c

Objectives

Methods

Results

Conclusion