The Research Institute at Fox Chase Cancer Center, Immune Cell Development and Host Defense Program, Philadelphia, Pennsylvania, USA
The Research Institute at Fox Chase Cancer Center, Immune Cell Development and Host Defense Program, Philadelphia, Pennsylvania, USA.
J Virol. 2015 Jan;89(1):776-83. doi: 10.1128/JVI.02176-14. Epub 2014 Oct 29.
It has been shown in various infection models that CD4(+) T cell help (TH) is necessary for the conditioning, maintenance, and/or recall responses of memory CD8(+) T cells (CD8M). Yet, in the case of vaccinia virus (VACV), which constitutes the vaccine used to eradicate smallpox and is a candidate vector for other infectious diseases, the issue is controversial because different groups have shown either T(H) dependence or independence of CD8M conditioning, maintenance, and/or recall response. In agreement with some of these groups, we show that T(H) plays a role in, but is not essential for, the maintenance, proliferation, and effector differentiation of polyclonal memory CD8(+) T cells after infection with wild-type VACV strain Western Reserve. More important, we show that unhelped and helped anti-VACV memory CD8(+) T cells are similarly efficient at protecting susceptible mice from lethal mousepox, the mouse equivalent of human smallpox. Thus, T(H) is not essential for the conditioning and maintenance of memory CD8(+) T cells capable of mounting a recall response strong enough to protect from a lethal natural pathogen. Our results may partly explain why the VACV vaccine is so effective.
We used vaccinia virus (VACV)--a gold standard vaccine--as the immunogen and ectromelia virus (ECTV) as the pathogen to demonstrate that the conditioning and maintenance of anti-VACV memory CD8(+) T cells and their ability to protect against an orthopoxvirus (OPV) infection in its natural host can develop in the absence of CD4(+) T cell help. Our results provide important insight to our basic knowledge of the immune system. Further, because VACV is used as a vaccine in humans, our results may help us understand how this vaccine induces protective immunity in this species. In addition, this work may partly explain why VACV is so effective as a vaccine.
在各种感染模型中已经表明，CD4(+) T 细胞辅助（TH）对于记忆 CD8(+) T 细胞（CD8M）的调理、维持和/或回忆反应是必要的。然而，对于痘苗病毒（VACV），它构成了用于根除天花的疫苗，并且是其他传染病的候选载体，这个问题存在争议，因为不同的小组已经表明 CD8M 的调理、维持和/或回忆反应依赖或不依赖于 T(H)。与其中一些小组一致，我们表明 T(H) 在野生型 VACV Western Reserve 株感染后多克隆记忆 CD8(+) T 细胞的维持、增殖和效应分化中起作用，但不是必需的。更重要的是，我们表明未辅助和辅助的抗 VACV 记忆 CD8(+) T 细胞在保护易感小鼠免受致死性鼠痘（人类天花的小鼠等效物）方面同样有效。因此，T(H)对于能够引发足以保护免受致死性天然病原体的回忆反应的记忆 CD8(+) T 细胞的调理和维持不是必需的。我们的结果可能部分解释了为什么 VACV 疫苗如此有效。
我们使用痘苗病毒（VACV）--一种黄金标准疫苗--作为免疫原，使用细疹病毒（ECTV）作为病原体，证明在缺乏 CD4(+) T 细胞辅助的情况下，抗 VACV 记忆 CD8(+) T 细胞的调理和维持及其抵抗其天然宿主中的正痘病毒（OPV）感染的能力可以发展。我们的结果为我们对免疫系统的基本知识提供了重要的见解。此外，由于 VACV 在人类中被用作疫苗，我们的结果可能有助于我们了解这种疫苗如何在该物种中诱导保护性免疫。此外，这项工作可能部分解释了为什么 VACV 作为疫苗如此有效。
