J Exper Med：揭示辅助T细胞抵御甲肝病毒感染的功能

辅助细胞通常被认为仅仅可以协助杀伤白细胞来进行保护机体的作用，但是近日刊登在国际杂志Journal of Experimental Medical上的一篇研究报告指出，辅助细胞或许是抵御甲型肝炎感染的“排头兵”。甲肝是一种由甲肝病毒引发的高度传染的肝病，尽管有有效的疫苗，可以每年世界上有上百万人都会感染甲肝病毒。

不像丙肝病毒，甲肝病毒不会建立持续性感染时期，然而在疾病预后还会有20%的病人甲肝疾病复发。研究者揭示，熟知的CD8+杀伤性T细胞在控制丙肝病毒和乙肝病毒感染上发挥着重要作用，这些T细胞可以通过杀灭被感染的肝脏细胞来发挥作用。虽然杀伤过程有损肝脏，可是对于遏制病毒增殖以及疾病的有效治疗却十分重要。

20年前的一项研究指出，杀伤性T细胞同样可以控制甲肝病毒的感染，然而Walker教授通过研究急性甲肝病毒感染的时候观察到了一种非常不同的免疫效应样式。他发现在有效地杀伤性T细胞产生之前感染可以被很好的控制，甲肝病毒的生长可以变成被CD4+辅助细胞来控制，辅助细胞是协助T细胞发挥免疫效应的一种细胞。在两个被甲肝病毒感染的动物机体中，辅助T细胞可以分泌很多银子来抑制病毒生长，当然在这个过程中也会促使肝脏发炎损伤。

另外研究者也发现辅助T细胞甲肝病毒的再产生再次反应，而且维持很长时间，知道病毒被彻底地清除出机体数个月后，这种反应才会逐渐减小至消失。研究人员的研究揭示了CD8+ T细胞对于控制甲肝病毒感染并不是必须的，另外CD4+ T细胞可以直接阻止病毒的复制和生长。如果CD4+ T细胞在人类机体中也有类似的作用的话，那么其有可能会成为抑制甲肝复发的一个新的靶点。

如果正如研究发现CD4+ T细胞确实具有免疫监督功能，那么高危复发病人或可以使用提高T细胞活性的疫苗，来使得病毒彻底的被杀灭。

编译自：Helper T Cells, Not Killer T Cells, Might Be Responsible for Clearing Hepatitis A Infection

doi:10.1084/jem.20111906
PMC:
PMID:

Dominance of the CD4+ T helper cell response during acute resolving hepatitis A virus infection

Yan Zhou1, Benoît Callendret1, Dan Xu1, Kathleen M. Brasky2, Zongdi Feng3,4,5,6,7, Lucinda L. Hensley3,4,5,6,7, Jeremie Guedj8,9, Alan S. Perelson8, Stanley M. Lemon3,4,5,6,7, Robert E. Lanford2,10, and Christopher M. Walker1,11

Hepatitis A virus (HAV) infection typically resolves within 4–7 wk but symptomatic relapse occurs in up to 20% of cases. Immune mechanisms that terminate acute HAV infection, and prevent a relapse of virus replication and liver disease, are unknown. Here, patterns of T cell immunity, virus replication, and hepatocellular injury were studied in two HAV-infected chimpanzees. HAV-specific CD8+ T cells were either not detected in the blood or failed to display effector function until after viremia and hepatitis began to subside. The function of CD8+ T cells improved slowly as the cells acquired a memory phenotype but was largely restricted to production of IFN-γ. In contrast, CD4+ T cells produced multiple cytokines when viremia first declined. Moreover, only CD4+ T cells responded during a transient resurgence of fecal HAV shedding. This helper response then contracted slowly over several months as HAV genomes were eliminated from liver. The findings indicate a dominant role for CD4+ T cells in the termination of HAV infection and, possibly, surveillance of an intrahepatic reservoir of HAV genomes that decays slowly. Rapid contraction or failure to sustain such a CD4+ T cell response after resolution of symptoms could increase the risk of relapsing hepatitis A.