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


RESULTS
We obtained blood from stroke patients and matching controls to perform flow cytometry and multiplex measurement of inflammatory mediators. Our data suggest a pronounced activation ofiNKT cells in stroke patients as compared with matched Healthy and Hospital control patients. The magnitude ofiNKT activation is positively correlated with the severity of stroke, supporting the hypothesis thatiNKT 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.


CONCLUSIONS
Stroke triggers a robust and sustained shift in systemic immunity in patients, including specific lymphopenia, robust activation ofiNKT 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.
Centre for Inflammatory Diseases, Department of Medicine, School of Clinical Science, Monash University, Melbourne, VIC, Australia; Department of Physiology and Pharmacology, Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada.
Connie H Y
CH
Wong
Department of Physiology and Pharmacology, Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada; Department of Critical Care, Snyder Institute for Critical Care, University of Calgary, Calgary, AB, Canada.
Craig N
CN
Jenne
Department of Critical Care, Snyder Institute for Critical Care, University of Calgary , Calgary, AB , Canada.
Patrick P
PP
Tam
Department of Critical Care, Snyder Institute for Critical Care, University of Calgary , Calgary, AB , Canada.
Caroline
C
Léger
Stroke Unit, Department of Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary , Calgary, AB , Canada.
Andres
A
Venegas
Stroke Unit, Department of Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary , Calgary, AB , Canada.
Karla
K
Ryckborst
Stroke Unit, Department of Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary , Calgary, AB , Canada.
Michael D
MD
Hill
Department of Physiology and Pharmacology, Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada; Department of Critical Care, Snyder Institute for Critical Care, University of Calgary, Calgary, AB, Canada.
Paul
P
Kubes
IL-10; iNKT cells; immune suppression; infection; stroke