Andrews Daniel M, Andoniou Christopher E, Fleming Peter, Smyth Mark J, Degli-Esposti Mariapia A
Immunology and Virology Program, Centre for Ophthalmology and Visual Science, The University of Western Australia, Western Australia, Australia.
J Virol. 2008 May;82(10):4931-7. doi: 10.1128/JVI.02127-07. Epub 2008 Mar 12.
Both innate and adaptive immune responses participate in the control of murine cytomegalovirus (mCMV) infection. In some mouse strains, like BALB/c, the control of infection relies on the activities of CD8(+) T cells. mCMV-specific CD8(+) T-cell responses are unusual in that, even after mCMV has been controlled in the periphery, the numbers of circulating virus-specific CD8(+) T cells remain high compared to those observed in other viral infections. To better understand the generation and maintenance of mCMV-specific CD8(+) T-cell responses, we evaluated how antigen load and effector molecules, such as perforin (Prf) and gamma interferon (IFN-gamma), influence these responses during acute infection in vivo. Viral burden affected the magnitude, but not the early kinetics, of antigen-specific CD8(+) T-cell responses. Similarly, the magnitude of virus-specific CD8(+) T-cell expansion was affected by Prf and IFN-gamma, but contraction of antigen-specific responses occurred normally in both Prf- and IFN-gamma-deficient mice. These data indicate that control of mCMV-specific CD8(+) T-cell expansion and contraction is more complex than anticipated and, despite the role of Prf or IFN-gamma in controlling viral replication, a full program of T-cell expansion and contraction can occur in their absence.
先天性免疫应答和适应性免疫应答均参与对小鼠巨细胞病毒(mCMV)感染的控制。在一些小鼠品系中,如BALB/c,感染的控制依赖于CD8(+) T细胞的活性。mCMV特异性CD8(+) T细胞应答不同寻常之处在于,即使mCMV在外周已得到控制,循环中的病毒特异性CD8(+) T细胞数量与在其他病毒感染中观察到的相比仍然很高。为了更好地理解mCMV特异性CD8(+) T细胞应答的产生和维持,我们评估了抗原负荷以及效应分子,如穿孔素(Prf)和γ干扰素(IFN-γ),在体内急性感染期间如何影响这些应答。病毒载量影响抗原特异性CD8(+) T细胞应答的强度,但不影响其早期动力学。同样,病毒特异性CD8(+) T细胞扩增的强度受Prf和IFN-γ的影响,但在Prf缺陷和IFN-γ缺陷小鼠中,抗原特异性应答的收缩均正常发生。这些数据表明,mCMV特异性CD8(+) T细胞扩增和收缩的控制比预期更为复杂,并且尽管Prf或IFN-γ在控制病毒复制中起作用,但在它们缺失的情况下,T细胞扩增和收缩的完整程序仍可发生。