title: A divergent response of innate regulatory T-cells to sepsis in humans: circulating invariant natural killer T-cells are preserved.
abstract: BACKGROUND
  Sepsis is associated with severe immunosuppression, evidenced by loss and dysfunction of CD3(+) lymphocytes and γδ-TCR(+) T-cells. There is limited data addressing changes in the invariant natural killer T-(iNKT) cell population with sepsis, and whether such changes correlate with clinical outcomes. Specifically, septic geriatric patients have marked mortality. How γδ-TCR(+) T-cells and iNKT-cells are altered in the settings of sepsis and advanced age, and how these changes correlate with mortality are unknown.
  
  
  METHODS
  49 young (18-50years) and 55 geriatric (>65years) ICU patients with confirmed sepsis were enrolled. Blood was stained with antibodies to detect the percentage and absolute number of CD3(+) (T-cells), γδ-TCR(+) T-cell, TCR-Vα-24(+) (iNKT-cells), and CD69(+) (marker of cell activation). Blood from 10 healthy controls was also collected.
  
  
  RESULTS
  Septic patients displayed marked leukocytosis, decreased CD3(+) lymphocytes, and γδ-TCR(+) T-cells, and increased percentage and number of iNKT-cells. Young and geriatric patients had similar degree of leukocytosis, along with percentage, number, and %CD69(+) CD3(+) T-cell and γδ-TCR(+) T-cells; however, percentage, number, and %CD69(+)iNKT-cells were most markedly elevated in geriatric patients. Geriatric non-survivors had higher percentage and number of, but decreased %CD69(+), iNKT-cells vs survivors.
  
  
  CONCLUSIONS
  iNKT-cells are increased in sepsis, suggesting that they typify an evolving morbid state. This is most pronounced in geriatric non-survivors, a group demonstrating dysfunctional regulatory iNKT-cell phenotype.
authors.affiliation: Division of Surgical Research, Department of Surgery, Warren Alpert Medical School of Brown University, Rhode Island Hospital, Providence, RI 02903, United States. Electronic address: dheffernan@brown.edu.
authors.forename: Daithi S
authors.initials: DS
authors.lastname: Heffernan
authors.affiliation: Division of Surgical Research, Department of Surgery, Warren Alpert Medical School of Brown University, Rhode Island Hospital, Providence, RI 02903, United States.
authors.forename: Sean F
authors.initials: SF
authors.lastname: Monaghan
authors.affiliation: Division of Surgical Research, Department of Surgery, Warren Alpert Medical School of Brown University, Rhode Island Hospital, Providence, RI 02903, United States.
authors.forename: Chun-Shiang
authors.initials: CS
authors.lastname: Chung
authors.affiliation: Division of Surgical Research, Department of Surgery, Warren Alpert Medical School of Brown University, Rhode Island Hospital, Providence, RI 02903, United States.
authors.forename: William G
authors.initials: WG
authors.lastname: Cioffi
authors.affiliation: Division of Geriatrics, Department of Medicine, Warren Alpert Medical School of Brown University, Rhode Island Hospital, Providence, RI 02903, United States.
authors.forename: Stefan
authors.initials: S
authors.lastname: Gravenstein
authors.affiliation: Division of Surgical Research, Department of Surgery, Warren Alpert Medical School of Brown University, Rhode Island Hospital, Providence, RI 02903, United States.
authors.forename: Alfred
authors.initials: A
authors.lastname: Ayala
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001775:Blood Circulation / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D007964:Leukocytosis / Q000276:immunology* / Q000401:mortality; D008213:Lymphocyte Activation; D008875:Middle Aged; D055611:Natural Killer T-Cells / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism; D018805:Sepsis / Q000276:immunology* / Q000401:mortality; D016019:Survival Analysis; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D055815:Young Adult
chemical_list: D011948:Receptors, Antigen, T-Cell; D016692:Receptors, Antigen, T-Cell, gamma-delta; C528689:Valpha24 protein, human