Innate T cells in the intensive care unit

Abstract

Rapid onset of acute inflammation is a hallmark of critical illnesses that bring patients to the intensive care unit (ICU). In critical illness, innate T cells rapidly reach full activation and drive a robust acute inflammatory response. As "cellular adjuvants," innate T cells worsen inflammation and mortality in several common critical illnesses including sepsis, ischemia-reperfusion injury, stroke, and exacerbations of respiratory disease. Interestingly, innate T cell subsets can also promote a protective and anti-inflammatory response in sepsis, ischemia-reperfusion injury, and asthma. Therapies that target innate T cells have been validated in several models of critical illness. Here, we review the role of natural killer T (NKT) cells, mucosal-associated invariant T (MAIT) cells and γδ T cells in clinical and experimental critical illness.

Keywords: Cardiac arrest; Critical care; Gamma delta T cell; MAIT cell; NKT cell; Sepsis.

Figure 1.. Innate T cells drive critical illness.

(A) Invariant NKT (iNKT) cells drive the production of inflammatory and immunosuppressive cytokines that worsen outcomes in experimental critical illnesses. IRI = ischemia-reperfusion injury. ARDS = acute respiratory distress syndrome. (B) γδ T cells drive the production of inflammatory cytokines that worsen outcomes in experimental sepsis and stroke.

Figure 2.. Innate T cells are therapeutic targets in critical illness.

(A) Treatment with altered lipid antigens (OCH), exogenous cytokines (IL-30) or ligands for immune checkpoint receptors (Tim-3) skew iNKT cells towards an anti-inflammatory phenotype and improve outcomes in experimental sepsis. (B) αGalCer antigen activates iNKT cells, which coordinate production of IFNγ and ameliorate post-burn and post-stroke immunosuppression. (C) Sulfatide antigen activates diverse NKT cells, which improve outcomes in experimental sepsis, ischemia-reperfusion injury (IRI) and asthma exacerbation.