The adaptor molecule MyD88 directly promotes CD8 T cell responses to vaccinia virus.
The adaptor molecule MyD88 directly promotes CD8 T cell responses to vaccinia virus.
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DOI：
10.4049/jimmunol.0803682
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发表时间：
2009-05-15
期刊：
影响因子：
--
通讯作者：
Salek-Ardakani S
中科院分区：
文献类型：
--
作者：
Zhao Y;De Trez C;Flynn R;Ware CF;Croft M;Salek-Ardakani S
痘苗病毒(VACV)能诱导强大的CD8T细胞应答，在宿主抵抗中起重要作用。到目前为止，关于产生大量VACV特异性效应CD8T细胞所必需的分子的信息很少。在这里，我们证明了接头分子MyD88对主要和次要VACV表位的初级CD8T细胞反应的大小至关重要。MyD88−/−小鼠在CD8T细胞扩增和抗病毒细胞因子的产生方面表现出显著的减少。令人惊讶的是，这一缺陷并不是由于抗原提呈细胞功能受损所致，因为MyD88CD8DC在VACV感染后能够正常成熟并能够促进强大的−/−T细胞启动。相反，过继转移实验表明，CD8T细胞中依赖MyD88的内在途径是至关重要的。MyD88缺陷的CD8T细胞在野生型宿主中不能聚集，病毒感染后导致MyD88缺陷的VACV特异性CD8T细胞增殖不良。相反，在缺乏TRIF、TLR2、TLR4、TLR9和IL-1R的情况下，没有明显的缺陷。总之，我们的结果强调了MyD88在最初的抗病毒CD8 T细胞反应中的重要作用，并表明靶向这一途径可能有助于促进和维持抗VACV免疫。
Vaccinia Virus (VACV) elicits a robust CD8 T cell response that plays an important role in host resistance. To date, there is little information on the molecules that are essential to generate large pools of VACV-specific effector CD8 T cells. Here, we show that the adaptor molecule MyD88 is critical for the magnitude of primary CD8 T cell responses to both dominant and subdominant VACV epitopes. MyD88−/− mice exhibit profound reduction in CD8 T cell expansion and anti-viral cytokine production. Surprisingly, the defect was not due to impaired antigen-presenting cell function, as MyD88−/− DC matured normally and were able to promote strong CD8 T cell priming following VACV infection. Rather, adoptive transfer experiments demonstrated that intrinsic MyD88-dependent pathways in CD8 T cells were critical. MyD88-deficient CD8 T cells failed to accumulate in wild-type hosts, and poor expansion of MyD88-deficient VACV-specific CD8 T cells resulted after virus infection. In contrast, no defect was evident in the absence of TRIF, TLR2, TLR4, TLR9, and IL-1R. Together, our results highlight an important role for MyD88 in initial anti-viral CD8 T cell responses and suggest that targeting this pathway may be useful in promoting and sustaining anti-VACV immunity.
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影响因子：
15.3
作者：
Harte, MT;Haga, IR;Maloney, G;Gray, P;Reading, PC;Bartlett, NW;Smith, GL;Bowie, A;O'Neill, LAJ
通讯作者：
O'Neill, LAJ
DOI：
10.1084/jem.20050821
发表时间：
2005-09-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Kolumam GA;Thomas S;Thompson LJ;Sprent J;Murali-Krishna K
通讯作者：
Murali-Krishna K
DOI：
10.1084/jem.20030162
发表时间：
2003-08-04
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Lund J;Sato A;Akira S;Medzhitov R;Iwasaki A
通讯作者：
Iwasaki A
影响因子：
4.4
作者：
Belz, GT;Shortman, K;Heath, WR
通讯作者：
Heath, WR
影响因子：
4.4
作者：
Gelman, AE;Zhang, JD;Turka, LA
通讯作者：
Turka, LA