Rani Meenakshi, Schwacha Martin G
Department of Surgery, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America.
PLoS One. 2017 Jun 2;12(6):e0179015. doi: 10.1371/journal.pone.0179015. eCollection 2017.
Burn-induced inflammation leads to impaired immune responses resulting in increased morbidity and mortality. T-cells are central in the immune response and circulating CD4 and CD8 T-cells have been used to evaluate immune status; however, the role of these T-cell subsets in the burn wound is unknown.
Male C57BL/6 mice were subjected to a major 3rd degree scald burn or sham treatment. Twenty-four hours later, full thickness skin samples from sham mice and the burn wounds were collected and single cells were isolated and analyzed for αβ TCR, γδ TCR, CD3, CD4, CD8 and CD69 expressions by flow cytometry.
The burn wound contained significantly greater numbers of T-cells than skin from sham mice, due to a profound infiltration of αβ T-cells. These infiltrating αβ T-cells were primarily suppressor T-cells with a CD8+ or CD8-CD4- phenotype. The 15-fold increase in CD8+ αβ T-cells caused a decrease in the CD4:CD8 ratio from 0.7 in sham skin to 0.3 in the burn wound. In contrast, the majority of the γδ T-cells in sham skin were CD4-CD8-, which decreased 9-fold in the burn wound. CD69 expression was suppressed on burn wound αβ T-cells, but increased on γδ T-cells in the burn wound.
The infiltrating burn wound αβ T-cells likely act to quell inflammation. In contrast wound γδ T-cells were activated with elevated CD4 and CD69 expression. Thus, these two distinct T-cell subsets likely differentially regulate the burn wound inflammatory response.
烧伤引起的炎症会导致免疫反应受损,从而增加发病率和死亡率。T细胞在免疫反应中起核心作用,循环中的CD4和CD8 T细胞已被用于评估免疫状态;然而,这些T细胞亚群在烧伤创面中的作用尚不清楚。
对雄性C57BL/6小鼠进行大面积三度烫伤或假手术处理。24小时后,收集假手术小鼠的全层皮肤样本和烧伤创面,分离单细胞,通过流式细胞术分析αβ TCR、γδ TCR、CD3、CD4、CD8和CD69的表达。
由于αβ T细胞的大量浸润,烧伤创面中的T细胞数量明显多于假手术小鼠的皮肤。这些浸润的αβ T细胞主要是具有CD8+或CD8-CD4-表型的抑制性T细胞。CD8+αβ T细胞增加15倍导致CD4:CD8比值从假手术皮肤中的0.7降至烧伤创面中的0.3。相比之下,假手术皮肤中的大多数γδ T细胞是CD4-CD8-,在烧伤创面中减少了9倍。烧伤创面αβ T细胞上的CD69表达受到抑制,但烧伤创面γδ T细胞上的CD69表达增加。
浸润到烧伤创面的αβ T细胞可能起到平息炎症的作用。相比之下,创面γδ T细胞被激活,CD4和CD69表达升高。因此,这两个不同的T细胞亚群可能对烧伤创面的炎症反应有不同的调节作用。