Abstract W P100: Alterations of γδT Cell Subsets in Stroke Patients with White Matter Disease

Abstract

Background: γδT cells have been shown in experimental models to play a role in the evolution of ischemic brain injury by increasing cerebral infarct volumes and neurological deficits. We have previously reported decreased levels of γδT cells in the subacute phase of human stroke. In this study we aimed to determine the functional significance of alterations in levels of γδT cells and other T cell subsets on the extent of ischemic brain injury. Methods: Blood was drawn from ischemic stroke patients within 24 hours of recruitment and stained with CD3 (PE-TR), γδTCR (PE), CD4 (FITC) and CD8 (PE-Cy5) monoclonal antibodies. γδT cells were also divided into functional subsets - CD4+ γδT, CD8+ γδT and null γδT cells. Percentages of circulating lymphocytes were measured by a fluorescent activated cell counter. The extent of acute ischemic injury was measured using lesion volume on diffusion weighted images by Image Processing Analysis and Visualization (MIPAV), while the extent of chronic ischemic injury which is manifested as white matter changes(WMC) was assessed using the Age Related White Matter Changes (ARWMC) rating score. Independent T-tests and non-parametric tests were used for between group comparisons. Results: Of the 41 patients recruited, the mean age was 66.8±13 years and 18 (43.9%) were men. Blood was drawn at a mean time of 47 ±30 hours after symptom onset. Compared to patients with absent-mild WMC (ARWMC score of 0-1), patients with moderate-severe WMC (ARWMC of 2-3) had higher percentages of CD8+ γδT cells (6.6% vs. 12.0%, p=0.005) and CD8+ T cells (22.2% vs. 28.5% p=0.036), and lower percentages of CD4+ T cells (71.0% vs. 63.5%, p=0.048) and null γδT cells (72.7% vs. 59.6%, p=0.03). However γδT percentages did not differ significantly. The volumes of acute ischemic stroke lesions did not correlate with γδT levels or with other T cell subsets. Conclusions: Alterations of T cell subsets, most notably, CD8+ γδT and CD8+ T cells were present in stroke patients with cerebral white matter disease. Their role in the formation of cerebral small vessel disease needs to be further studied.