Gamma Delta T Cells Regulate Wound Myeloid CELL Activity After Burn

Abstract

Major burns induce immune complications, which are associated with myeloid cell activation by ill-defined mechanisms. While γδ T-cells have been shown to be important in post-injury inflammation and wound healing, their role in the regulation of myeloid cells remains unknown. To study this wildtype (WT) and γδ T-cell deficient (δTCR−/−) mice were subjected to major burn (25% TBSA, 3rd degree) or sham treatment. At 3 days thereafter, skin samples were assayed for cytokine content or used to isolate single cells that were used for myeloid cell characterization by flow cytometry. The number of CD11b+ myeloid cells increased by ~75% in the wound skin of WT mice. This influx was due to increased myeloid-derived suppressor cells (MDSC; CD11b+ GR1+), who’s numbers increased 19-fold compared to sham skin. In contrast, macrophage (MØ; CD11b+ F4/80+) numbers decreased by ~50% after burn. In δTCR−/− mice, burn increased the myeloid cell numbers ~5-fold. The increase in myeloid cells at the injury site of δTCR−/− mice was due to both a MDSC (50-fold) and a MØ (2-fold) influx. Burn increased skin cytokine levels for a number of prototypic inflammatory cytokines (IL-1β, IL-6, TNF-α, MIP-1β etc). TNF-α, MIP-1 α and MIP-1β levels were further elevated (2–3 fold) in the injured skin of δTCR−/− mice, as compared with WT mice. In conclusion these data show that γδ T-cells regulate myeloid cell infiltration of the wound site and act to quell inflammation, thereby promoting the transition to the proliferative phase of wound healing.

Damage-associated molecular patterns (DAMPs) released after burn are associated with inflammation and monocyte activation

“…We have previous shown that CD11b + population increases in the burn wound with a shift towards the CD11b high population [27]. A shift towards the CD11b high population was not observed in the study herein, which is likely related to the source of the cells (injury site vs. circulation) and the time post-injury (3 days vs. 24 hrs).…”

The composition of T-cell subsets are altered in the burn wound early after injury

“…Our laboratory has demonstrated an important role for T-cells in the burn wound inflammatory milieu, recruitment of immune cells to the injury site and healing [8–10, 21]. Based on this central role of T-cells in the burn wound, the current study was performed to further characterize the wound T-cell populations.…”

Antiviral Innate Immune Activation in HIV-Infected Adults Negatively Affects H1/IC31-Induced Vaccine-Specific Memory CD4+T Cells

“…Searching the literature, we found that cells involved in wound healing like alternatively activated macrophages (26), ␥␦-T cells (27), monocyte-derived multipotential cells (28), fibrocytes (17), and endothelial progenitor cells (29) have all been described to express these particular genes.…”