摘要
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。
To reveal the role of TNF-α in regulating the CD8^+T cell response in Listeria monocytogenes(LM)infection model, we immunized TNF-α knockout(KO) mice and wide type(WT) mice with OVA recombinant LMOVA, and determined the dynamic change of the OVA-specific CD8^+T cell response post infection. We found thatthe primary response in TNF-α KO mice was lower than that of WT mice, while CD8^+T cell contraction in TNF-αKO mice decreased slower than that of WT mice, and more memory cells were generated in TNF-α KO micecompared with WT mice. Compared to WT mice, the memory CD8^+T cells in TNF-α KO mice showed an increase ofspecific killing in vivo, which indicated that memory CD8^+T cells in TNF-α KO mice had comparable cytotoxicability with those in WT mice. We also determined the expression of some differentiation makers, and found that theratio of KLRG-1^+CD127^-CD62L-effective memory cells in memory CD8^+T cells were increase in TNF-α KO mice.Moreover, we found the expression of KLRG-1 and CD127 in effective CD8^+T cells showed no significant differencebetween TNF-α KO mice and WT mice on day 7 post infection, indicating that TNF-α did not impact early effective CD8^+T cell differentiation. These results indicate that TNF-α could regulate CD8^+T cell contraction and memory generation, and more effective memory cells exist in TNF-α KO mice might due to the anti-apoptosis effect of TNF-α KO during contraction phase.
出处
《免疫学杂志》
CAS
CSCD
北大核心
2016年第9期762-767,共6页
Immunological Journal
基金
湖南省自然科学基金(2016JJ2113,14JJ3104)
湖南省科技计划(2014TT2012)
南华大学博士启动基金(2014XQD40)
关键词
李斯特菌
应答收缩期
效应记忆细胞
Listeria monocytogenes
Response contraction phase
Effective memory cells