Abstract TP460: Regulatory T-Cells and CD4+ T Helper Cell Subsets Are Differentially Regulated and Express Distinct Activation States After Aneurysmal Subarachnoid Hemorrhage (SAH) and During Post-SAH Complications

Abstract

Background: Aneurysmal subarachnoid hemorrhage (SAH) is associated with high morbidity and mortality. Devastating post-SAH complications after aneurysm treatment lead to poor clinical outcome. Current research suggests critical role of inflammation during early and delayed brain injury phases over which these complications arise. T helper cells can polarize to multiple functionally unique subsets. Here, we investigate different CD4+ T cell subsets during these brain injury phases after SAH and their dynamics during post-SAH complications. Methods: Anticoagulated peripheral venous blood was obtained from 15 SAH patients on days 1 and 7, and once from healthy controls. After erythrocyte lysis and single cell wash, 1 million cells were stained with different anti-human mouse monoclonal antibodies and were acquired on BD LSR Fortessa. Lymphocytes were gated based on low side scatter and high CD45 expression. Different CD3+CD4+ T cell subsets were characterized by differential cell surface expression of CXCR3 and CCR6 into Th1, Th2, Th17, whereas Tregs by CD25 hi and CD127 lo . SAH patients were dichotomized based on presence or absence of different post-SAH complications (hydrocephalus, seizures, CVS, cerebral ischemia) to assess association of T cell subsets with these complications. Results: Total CD4+ T cells were significantly increased after SAH. Interestingly, Th2 cells were significantly decreased and Th17 cells increased on day 7 compared to day 1 after SAH. However, regulatory T-cells were significantly increased on both assessment days compared to controls. The analysis of activation states was done by CD38 and HLA-DR expression. Th1 and Treg cells were significantly increased on day 1 in SAH patients who developed seizures and CVS, respectively. HLA-DR + CD38 + Th2 cells significantly increased on day 1 in SAH patients who developed hydrocephalus, whereas HLA-DR - CD38 - Th1 cells significantly increased on day 1 in patients with infections. HLA-DR - CD38 - Treg cells were significantly reduced on day 1 and day 7 in patients developing cerebral ischemia . Conclusion: CD4+ T cell subsets and Treg cells display dynamic patterns after SAH, and show a distinct pattern of polarization and activation states in specific post-SAH complications.