Prolonged Activation of Invariant Natural Killer T Cells and TH2-Skewed Immunity in Stroke Patients

Abstract

BackgroundInfection is highly prevalent and contribute significantly to mortality of stroke patients. In addition to the well described robust systemic lymphocytopenia and skewed T helper 2 (TH2)-immunity after stroke, emerging experimental evidence demonstrate that the development of infection poststroke is attributed by the activation of invariant natural killer T (iNKT) cells. In this prospective study, we examined the levels of a broad spectrum of inflammatory mediators, the activation status of iNKT cell in the blood of patients with various degree of stroke severity, and investigate whether these parameters differ in patients who later develop poststroke infections.Methods and resultsWe obtained blood from stroke patients and matching controls to perform flow cytometry and multiplex measurement of inflammatory mediators. Our data suggest a pronounced activation of iNKT cells in stroke patients as compared with matched Healthy and Hospital control patients. The magnitude of iNKT activation is positively correlated with the severity of stroke, supporting the hypothesis that iNKT cells may contribute in the modulation of the host immune response after stroke-associated brain injury. In addition, stroke severity is closely correlated with decreased TH1/TH2 ratio, increased production of interleukin (IL)-10, with infected stroke patients showing exacerbated production of IL-10.ConclusionStroke triggers a robust and sustained shift in systemic immunity in patients, including specific lymphopenia, robust activation of iNKT cells, systemic production of IL-10, and a prolonged TH2-skewed immunity, all are potential contributors to severe immune suppression seen in patients after stroke. Future studies with large sample size will provide potential causality relationship insights.

Dynamic Cerebral Autoregulation Post Endovascular Thrombectomy in Acute Ischemic Stroke

“…We found that patients with complete (TICI 3) recanalization after the thrombectomy had less severe impairments in their autoregulation than patients with incomplete recanalization (TICI 2a or 2b). Impairments in autoregulation were primarily observed 24 to 96 h after the LSW time and were bilateral, affecting both the ipsilateral and contralateral hemispheres, supporting prior work demonstrating the presence of global impairments in autoregulation after an ischemic stroke [ 10 , 13 , 37 ]. However, some prior studies have demonstrated the presence of unilateral impairments in cerebral autoregulation [ 12 , 38 , 39 ], suggesting an element of interpatient variability, with some suggesting that large-vessel atherosclerosis and small-vessel disease likely contribute to bilateral impairments [ 37 , 39 ].…”

“…For example, post-stroke impairment in autoregulation has been associated with poor outcomes, including larger infarct volumes and increased rates of hemorrhagic conversion. These impairments are particularly prominent within the first five days post stroke [ 10 , 11 ], and appear to be global, affecting both the ipsilateral and the contralateral hemispheres [ 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 ].…”

High serum OX40 ligand correlates with severity and mortality in patients with massive cerebral infarction

“…[ 23 ] Second, ischemic stroke triggers sustained and stable changes in the systemic immune system, including specific lymphopenia, excessive production of IL-10, and prolonged Th2 biased immunity, all of which lead to severe immunosuppression in stroke patients. [ 24 ] The OX40L-OX40 pathway could enhance Th2 responses, and this indicates that patients with high serum OX40L have high likelihood to develop low immune function and are prone to various infections. [ 25 ] In this article, nonsurvivors of CI patients showed significantly higher rate of pulmonary infection than survivors.…”

The evolving role of neuro‐immune interaction in brain repair after cerebral ischemic stroke

“…However, the subgroups of T cells that promote neurogenesis were not identified. In fact, there are huge discrepancies with respect to cytokine production from Th1 or Th2 cells and the ratio of Th1/Th2 cells can even affect stroke severity . Th17 cells and γδ T cells produce pro‐inflammatory cytokines and chemokines, usually impairing neurogenesis .…”