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Front Immunol. 2015 Aug 12;6:401. doi: 10.3389/fimmu.2015.00401. eCollection 2015.

CD1d- and MR1-Restricted T Cells in Sepsis.

Frontiers in immunology

Peter A Szabo, Ram V Anantha, Christopher R Shaler, John K McCormick, S M Mansour Haeryfar

Affiliations

  1. Department of Microbiology and Immunology, Western University , London, ON , Canada.
  2. Department of Microbiology and Immunology, Western University , London, ON , Canada ; Division of General Surgery, Department of Medicine, Western University , London, ON , Canada.
  3. Department of Microbiology and Immunology, Western University , London, ON , Canada ; Centre for Human Immunology, Western University , London, ON , Canada ; Lawson Health Research Institute , London, ON , Canada.
  4. Department of Microbiology and Immunology, Western University , London, ON , Canada ; Centre for Human Immunology, Western University , London, ON , Canada ; Lawson Health Research Institute , London, ON , Canada ; Division of Clinical Immunology and Allergy, Department of Medicine, Western University , London, ON , Canada.

PMID: 26322041 PMCID: PMC4533011 DOI: 10.3389/fimmu.2015.00401

Abstract

Dysregulated immune responses to infection, such as those encountered in sepsis, can be catastrophic. Sepsis is typically triggered by an overwhelming systemic response to an infectious agent(s) and is associated with high morbidity and mortality even under optimal critical care. Recent studies have implicated unconventional, innate-like T lymphocytes, including CD1d- and MR1-restricted T cells as effectors and/or regulators of inflammatory responses during sepsis. These cell types are typified by invariant natural killer T (iNKT) cells, variant NKT (vNKT) cells, and mucosa-associated invariant T (MAIT) cells. iNKT and vNKT cells are CD1d-restricted, lipid-reactive cells with remarkable immunoregulatory properties. MAIT cells participate in antimicrobial defense, and are restricted by major histocompatibility complex-related protein 1 (MR1), which displays microbe-derived vitamin B metabolites. Importantly, NKT and MAIT cells are rapid and potent producers of immunomodulatory cytokines. Therefore, they may be considered attractive targets during the early hyperinflammatory phase of sepsis when immediate interventions are urgently needed, and also in later phases when adjuvant immunotherapies could potentially reverse the dangerous state of immunosuppression. We will highlight recent findings that point to the significance or the therapeutic potentials of NKT and MAIT cells in sepsis and will also discuss what lies ahead in research in this area.

Keywords: CD1d; LPS; MAIT cell; MR1; NKT cell; infection; sepsis; α-galactosylceramide

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