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目的探讨TNF-α在李斯特菌(Listeria monocytogenes,LM)感染模型中对CD8~+T细胞应答的影响。方法采用尾静脉注射重组OVA的李斯特菌株感染TNF-α基因敲除(TNF-αKO)小鼠和野生型(WT)对照小鼠建立系统性感染模型。运用流式细胞术检测不同时相点TNF-αKO小鼠和WT小鼠中内源性和外源性特异性CD8+T细胞应答反应情况。采用体内细胞杀伤实验和检测细菌滴度的方法评估TNF-αKO小鼠和WT小鼠感染后记忆期CD8~+T细胞的效应功能。接着分析记忆期和增殖期CD8~+T细胞的KLRG-1和CD127等分子的表达变化。结果与WT对照小鼠相比,TNF-αKO小鼠中CD8~+T细胞应答减少,记忆细胞增多;TNF-αKO小鼠中记忆CD8~+T细胞的效应功能正常;TNF-αKO小鼠记忆CD8~+T细胞中含有更多比例的KLRG-1+CD127-CD62L-效应记忆细胞,而第7天TNF-αKO小鼠特异性CD8~+T细胞的KLRG-1和CD127的表达与对照组无明显差别。结论TNF-αKO小鼠初次应答降低,形成更多记忆细胞,且效应记忆细胞增多。其机制与早期效应CD8~+T细胞分化无关,可能是TNF-αKO小鼠更多的KLRG-1+CD127-细胞在应答收缩期存活所致。
Objective To investigate the effect of TNF-α on the response of CD8 + T cells in Listeria monocytogenes (LM) infection model. Methods TNF-α knockout (TNF-α knockout) mice and wild type (WT) control mice were infected with Listeria monocytogenes injected with tail vein into recombinant OVA to establish a systemic infection model. Flow cytometry was used to detect the endogenous and exogenous specific CD8 + T cell responses in TNF-α KO mice and WT mice at different time points. The in vivo cytotoxicity assay and the detection of bacterial titer were used to assess the effector function of memory CD8 ~ + T cells in TNF-α KO mice and WT mice. Then we analyzed the expressions of KLRG-1 and CD127 on CD8 + T cell in memory and proliferative phase. Results Compared with WT control mice, the response of CD8 + T cells in TNF-α KO mice decreased and the memory cells increased. The effect of memory CD8 + T cells in TNF-α KO mice was normal. The memory of TNF-α KO mice The percentage of KLRG-1 + CD127-CD62L-effector cells was higher in CD8 ~ + T cells, while the expression of KLRG-1 and CD127 in TNF-α KO mouse-specific CD8 ~ + T cells on day 7 was significantly higher than that in control group No significant difference. Conclusions The initial response of TNF-α KO mice is reduced, more memory cells are formed and the number of effector memory cells is increased. The mechanism is independent of early differentiation of CD8 ~ + T cells. It is likely that more KLRG-1 + CD127- cells in TNF-α KO mice survive in response to systole.