CD4~+CD25~+调节性T细胞对啮齿类疟原虫感染过程及结局的影响

目的探讨CD4+CD25+调节性T细胞数量在约氏疟原虫(致死型)和夏氏疟原虫混合感染小鼠免疫应答中的动态变化。方法DBA/2和BALB/c小鼠分别经腹腔注射致死型约氏疟原虫(P.y17XL)、夏氏疟原虫(P.cAS)和P.y17XL+P.cAS(1∶1)混合感染的红细胞,计数红细胞感染率;采用流式细胞术动态检测脾细胞中Tregs细胞数量的变化。结果P.y17XL+P.cAS感染的DBA/2小鼠于感染后18d自愈;而BALB/c小鼠于感染过程中虽然出现死亡(8d),但与P.y17XL感染小鼠(5d)相比,死亡时间明显延迟;P.y17XL和P.y17XL+P.cAS感染的DBA/2鼠于感染后第5d CD4+CD25+调节性T细胞数量均达峰值,随后缓慢下降,相比P.cAS感染的DBA/2鼠于感染后第10d达峰值,是其它两种同天感染鼠的3倍和2倍,且小鼠全部死亡;而P.y17XL和P.y17XL+P.cAS感染的BALB/c小鼠CD4+CD25+调节性T细胞数量于感染后均迅速升高,分别于感染后第5d和第8d达30%左右,小鼠全部死亡,相比P.cAS感染的BALB/c小鼠CD4+CD25+调节性T细胞数量于感染后缓慢升高,于感染后第5d达14%,随后开始下降。结论①P.y17XL+P.cAS混合感染DBA/2鼠后CD4+CD25+调节性T细胞数量的动态变化与P.y17XL单独感染表现出完全相同的模式;BALB/c鼠:CD4+CD25+调节性T细胞数量的动态变化与P.y17XL单独感染也表现出完全相同的模式,但变化的时间明显被滞后;②CD4+CD25+调节性T细胞的异常升高与感染结局密切相关。

Influence of CD4+CD25+ regulatory T cells on the course and outcome of infection with rodent plasmodium

To investigate the dynamic changes of CD4+CD25+ regulatory T cells in a mixed infection of mouse with Plasmodium yoelii and Plasmodium chabaudi,DBA/2 and BALB/c mice were injected intra-peritoneally with the parasitized erythrocytes using the lethal type of P.yoelii(P.y17XL) and P.chabaudi(P.cAS) as well as the mixed infection of P.y17XL plus P.cAS(1∶1).Then,the radio of the infected RBC was countered and the numbers of CD4+CD25+ regulatory T cells in spenocytes were detected dynamically by flow cytometry.It was found that DBA mice with mixed infection spontaneously cured 18 days after infection,while in BALB/c mice,although death occurred at 8 days after infection,moreover,in comparison with mice infected with P.y17XL(death occurred at 5 says after infection),the time of death was obviously delayed.The numbers of CD4+CD25+ regulatory T cells of DBA mice infected with P.y17XL and P.y17XL plus P.cAS approached their peaks at 5 days after infection and then declined gradually,meanwhile,those of mice infected with P.cAS reached its peak on 10 days post-infection,exhibited 3 times and 2 times higher in numbers in comparison with those of the other infected mice at the same day and all the mice died.Howover,the numbers of CD4+CD25+ regulatory T cells in BALB/c infected with P.y17XL and P.y17XL plus P.cAS appeared significant increase,approaching up to 30% of the total CD4+ T cells on 5 and 8 days post-infection(P<0.01).Those of BALB/c mice infected with P.cAS increased slowly approaching to 14% of the total CD4+ T cells on 5 days post-infection.From these observations,it is evident that the abonormal rise in the number of CD4+CD25+ regulatory T cells in infection with plasmodium may be related to the outcome of infection.