Murine cytomegalovirus interference with antigen presentation has little effect on the size or the effector memory phenotype of the CD8 T cell response
Murine cytomegalovirus interference with antigen presentation has little effect on the size or the effector memory phenotype of the CD8 T cell response
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DOI：
10.4049/jimmunol.172.11.6944
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发表时间：
2004-06-01
影响因子：
4.4
通讯作者：
Hill, AB
中科院分区：
文献类型：
--
作者：
Gold, MC;Munks, MW;Hill, AB
与大多数疱疹病毒一样，CMV编码抑制Ag呈递至CD 8 T细胞（VIPRs）的病毒基因。VIPR功能被认为是CMV建立其特征性的宿主终身感染所必需的。我们比较了用野生型鼠CMV（MCMV）和缺乏MCMV的三种已知VIPRs（m4、m6和m152）的病毒感染C57 BL/6小鼠。在急性感染期间，两种病毒在病毒复制和清除的动力学或病毒特异性CD 8 T细胞应答的大小和动力学方面几乎没有差异。在慢性感染期间，两种感染均维持了大量效应记忆病毒特异性CD 8 T细胞群（CD 8（低）-CD 62 L（-）CD 11 c（+）NKG 2A（+））;对两种病毒的CD 8 T细胞应答的大小和表型非常相似。CD 8 T细胞的特征性效应记忆表型表明野生型和Deltam 4 +m6+ m152病毒在感染的慢性期期间继续将Ag呈递给CD 8 T细胞。在感染的慢性期，MCMV不能从免疫活性小鼠中分离出来。然而，在免疫抑制后，Deltam 4 +m6+ ml 52和野生型病毒都可以从感染6周的小鼠中重新激活。因此，恢复CD 8 T细胞检测MCMV的能力对MCMV感染的过程和CD 8 T细胞对它的反应几乎没有明显的影响。这些结果挑战了VIPR功能是CMV在宿主中持续存在所必需的概念。
As with most herpesviruses, CMVs encode viral genes that inhibit Ag presentation to CD8 T cells (VIPRs). VIPR function has been assumed to be essential for CMV to establish its characteristic lifetime infection of its host. We compared infection of C57BL/6 mice with wild-type murine CMV (MCMV) and a virus lacking each of MCMV's three known VIPRs: m4, m6, and m152. During acute infection, there was very little difference between the two viruses with respect to the kinetics of viral replication and clearance, or in the size and kinetics of the virus-specific CD8 T cell response. During chronic infection, a large, effector memory, virus-specific CD8 T cell population (CD8(low)-CD62L(-)CD11c(+)NKG2A(+)) was maintained in both infections; the size and phenotype of the CD8 T cell response to both viruses was remarkably similar. The characteristic effector memory phenotype of the CD8 T cells suggested that both wild-type and Deltam4+m6+ml52 virus continued to present Ag to CD8 T, cells during the chronic phase of infection. During the chronic phase of infection, MCMV cannot be isolated from immunocompetent mice. However, upon immunosuppression, both Deltam4+m6+ml52 and wild-type virus could be reactivated from mice infected for 6 wk. Thus, restoring the ability of CD8 T cells to detect MCMV had little apparent effect on the course of MCMV infection and on the CD8 T cell response to it. These results challenge the notion that VIPR function is necessary for CMV persistence in the host.