鼠巨细胞病毒对小鼠调节性T细胞分化和效应性T细胞活化的影响

摘要

Objective To investigate the influence of murine cytomegalovirus on the expansion of CD+CD25+ Foxp3+ regulatory T cell (Treg) and the activation of CD4+ CD25+Foxp3 - effector T cell (TE) in vivo. Methods Forty-two BALB/c mice were intraperitoneally inoculated with appropriate amount ofMCMV Smith strain for establishing the model of infection, another 42 mice served as mocked-infected con-trois. Day 28 post MCMV infection was determined to be the demarcation point of the acute and chronic in- fection based on the viral load of major visceral organs. On day 1,3, 7, 14, 28, 45 and 60 post infection, splenocytes were prepared by means of routine method. The proportions of CD4+CD25+ Foxp3+Treg and CD4+CD25+Foxp3- activated TE in T lymphocyte were measured by flow cytometry. Results The propor- tion of CD+CD25+ Foxp3+ T cells in T lymphocytes was persistently suppressed since day 7 post infection, and fell to the lowest level on day 28 post infection (P <0.01), then zoomed and reached the peak value on day 60 post infection (P < 0.05). CD4+CD25+ Foxp3 - TE proportion was up to the highest on day 3 post infection(P < 0. 01), then suppressed and in significantly lower level since day 45 post infection (P < 0.05). Treg/CD+TE ratio was in lower level on day 3 to 14 post infection(P <0.05) ; but on day 45 and day 60 post infection Treg/CD+ TE ratio was markedly increased (P < 0.05). Conclusion MCMV infec- tion can increase the CD+CD25+Foxp3+ Treg proportion, and inhibit CD4+T cells activation in chronic in- fection phase, which is likely to suppress the function of antiviral immunity in the infected host to cause a persistent latent infection.%目的 在整体水平探讨小鼠巨细胞病毒(MCMV)感染对小鼠调节性T细胞(Treg)亚群CD4+CD25+Foxp3+T细胞分化和CD4+CD25+Foxpp3-效应性T细胞(TE)活化的影响.方法 建立全身播散型MCMV感染小鼠模型,依据主要脏器内病毒滴度,确定感染后第28天为本模型急、慢性期界定点.42只小鼠分别于感染MCMV后第1、3、7、14、28、45和60天处死6只;另设42只小鼠作为对照.流式细胞术检测CD4+CD25+F0xp34+Treg和活化的CD4+CD25+Foxp3-TE在脾单个核细胞中所占比率变化.结果 MCMV感染急性期CD4+CD25+Foxp3+Treg比率持续降低,第28天左右降至最低值,与对照组比较差异有统计学意义(P<0.01);随后直线上升,第45天高于基线,第60天升至峰值,与对照组比较差异有统计学意义(P<0.05);CD4+CD25+Foxp3-TE在感染后第3～7天高于对照组(P<0.05),其后持续下降,在感染后第45天和第60天显著低于对照组水平(P<0.05).Treg/CD4+CD25+TE比率在感染后第3～14天显著降低(P<0.05);随后逐渐上升,在感染后第45天和第60天均显著高于对照组(P<0.05).结论 MCMV可在慢性感染期诱导CD4+CD25+Foxp3+Treg种群扩增,抑制CD4+CD25+Foxp3-Treg活化增殖,这可能是MCMV逃避特异性免疫而实现长期潜伏的机制之一.