Activation of murine γδ T-cells by mitochondrial damage-associated molecular patterns (DAMPS) (45.4)

Abstract

Abstract Gamma delta T-cells have been shown to be important in the early immunoinflammatory response to injury, which can be independent of infection. This sterile inflammatory response is in part associated with DAMPs. Mitochondrial DAMPs (MTDs) have been shown to be important in trauma-induced neutrophil activation, but it is unknown whether MTDs activate other innate immune cells, such as γδ T-cells. To study this, splenic CD3+ γδ T-cells were isolated from αβ T-cell deficient C57BL/6 mice and mitochondria isolated from wildtype mouse livers. MTDs were isolated from mitochondria by sonication and centrifugation. Gamma delta T-cells were incubated with various concentrations of MTDs (0-1000 µg/ml) for 24 hr. T-cells were phenotyped for Toll-like receptor (TLR) expression by flow cytometry and the supernatants assayed for cytokine and growth factor content. MTDs caused a dose-dependent increase in TLR-2 and TLR-4 expression by γδ T-cells. Both the percentage of cells positive for TLRs and the degree of expression increased. MTDs also induced the dose-dependent production of the chemokine RANTES and the growth factors FGF and VEGF. These findings support the concept that the MTDs released after tissue/cellular injury are capable of activating γδ T-cells, thus initiating sterile inflammation as well as subsequent healing processes.