Article
Peripheral blood T-cell polarisation and their therapeutic implications after aneurysmal subarachnoid haemorrhage (aSAH)
Periphere T-Zellen Polarisation und deren therapeutische Implikationen nach aneurysmatischer Hirnblutung
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Published: | June 26, 2020 |
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Objective: Aneurysmal subarachnoid hemorrhage (aSAH) is associated with significant morbidity and mortality even after successful treatment of the bleeding aneurysm. Devastating complications occurring after SAH contribute mainly to poor clinical outcome. The current state of the knowledge suggests the indispensable role of sterile inflammation during early and delayed brain injury phases over which these complications arise. T-cells are fundamental part of adaptive immunity that can polarize to different sub-populations with different functional roles. Here, we investigate the role of different CD4+ T cell subsets and Treg cells during early and delayed brain injury after SAH.
Methods: Peripheral venous blood anticoagulated with EDTA was obtained from 15 SAH patients on day 1 and day 7, and once from healthy controls for multicolour flowcytometry. After erythrocyte lysis and a single cell wash, 1 million cells in 100 µL of FACS buffer were stained with different anti-human mouse monoclonal antibodies for 20 mins on ice. Cells were washed and final volume was adjusted to 500 µL. Cells were then acquired on LSR Fortessa (BD Biosciences, CA, USA). Lymphocytes were gated based on their low side scatter and high CD45 expression. Different subsets of CD3+ CD4+ T cells were characterized by differential cell surface expression of CXCR3 and CCR6 into Th1, Th2, Th17, whereas Tregs by CD25hi and CD127lo.
Results: Total number of CD4+ T cells was significantly increased after SAH. Interestingly, T helper-2 (Th2) cells were significantly decreased on day 7, whereas Th17 cells were increased compared to day 1 post-SAH. Regulatory T (Tregs) cells were significantly increased on both assessment days compared to controls. All T cell sub-populations (assessed by CD38 and HLA-DR expression) revealed a distinct activation state during the phases of early brain injury and delayed phase.
Conclusion: Subarachnoid hemorrhage leads to imbalance of anti-inflammatory T helper-2 (Th2) and pro-inflammatory T helper-1 (Th1) cells. Increase in Th1 cells and decrease in Th2 cells may exacerbate inflammation and contribute to post-SAH complications. T cell polarization could be potential target to ameliorate sterile inflammation after aSAH.