A divergent response of innate regulatory T-cells to sepsis in humans: Circulating invariant natural killer T-cells are preserved

摘要

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.