Vaccine-Elicited CD8+ T Cells Protect against Respiratory Syncytial Virus Strain A2-Line19F-Induced Pathogenesis in BALB/c Mice
Vaccine-Elicited CD8+ T Cells Protect against Respiratory Syncytial Virus Strain A2-Line19F-Induced Pathogenesis in BALB/c Mice
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DOI：
10.1128/jvi.01770-12
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发表时间：
2012-12-01
影响因子：
5.4
通讯作者：
Moore, Martin L.
中科院分区：
文献类型：
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作者：
Lee, Sujin;Stokes, Kate L.;Moore, Martin L.
CD 8（+）T细胞可能有助于呼吸道合胞病毒（RSV）的疫苗。与响应RSV感染的CD 8（+）T细胞相比，疫苗诱导的抗RSV CD 8（+）T细胞的定义不太明确。我们使用肽疫苗来检验疫苗诱导的RSV特异性CD 8（+）T细胞对RSV发病机制具有保护作用的假设。用代表免疫显性CD 8表位的M2（82-90）肽、Toll样受体（TLR）激动剂聚（I. C）和共刺激抗CD 40抗体的混合物（先前称为TriVax）处理BALB/c小鼠。TriVax疫苗接种诱导有效的效应抗RSV CD 8（+）细胞毒性T淋巴细胞（CTL）。用RSV毒株A2 line 19 F攻击小鼠，RSV毒株A2 line 19 F是导致气道粘蛋白表达的RSV发病机制模型。在接种疫苗后6天激发时，保护小鼠免受RSV感染和RSV诱导的气道粘蛋白表达和细胞性肺部炎症。与单独的A2 line 19 F感染相比，TriVax疫苗接种后进行攻击导致效应CD 8（+）T细胞具有更高的细胞因子表达，并且RSV特异性CD 8（+）T细胞在肺中更快地出现。当在TriVax疫苗接种后42天进行攻击时，记忆性CD 8（+）T细胞被RSV特异性四聚体应答引发，相当于TriVax诱导的效应CD 8（+）T细胞。这些记忆性CD 8（+）T细胞的细胞因子表达低于效应性CD 8（+）T细胞，并且在记忆阶段对A2 line 19 F的保护是部分的。我们发现疫苗诱导的效应抗RSV CD 8（+）T细胞保护小鼠免受RSV感染和发病，并且保护作用的减弱与CD 8（+）T细胞细胞因子表达的降低相关。
CD8(+) T cells may contribute to vaccines for respiratory syncytial virus (RSV). Compared to CD8(+) T cells responding to RSV infection, vaccine-elicited anti-RSV CD8(+) T cells are less well defined. We used a peptide vaccine to test the hypothesis that vaccine-elicited RSV-specific CD8(+) T cells are protective against RSV pathogenesis. BALB/c mice were treated with a mixture (previously termed TriVax) of an M2(82-90) peptide representing an immunodominant CD8 epitope, the Toll-like receptor (TLR) agonist poly(I.C), and a costimulatory anti-CD40 antibody. TriVax vaccination induced potent effector anti-RSV CD8(+) cytotoxic T lymphocytes (CTL). Mice were challenged with RSV strain A2line19F, a model of RSV pathogenesis leading to airway mucin expression. Mice were protected against RSV infection and against RSVinduced airway mucin expression and cellular lung inflammation when challenged 6 days after vaccination. Compared to A2line19F infection alone, TriVax vaccination followed by challenge resulted in effector CD8(+) T cells with greater cytokine expression and the more rapid appearance of RSVspecific CD8(+) T cells in the lung. When challenged 42 days after TriVax vaccination, memory CD8(+) T cells were elicited with RSVspecific tetramer responses equivalent to TriVaxinduced effector CD8(+) T cells. These memory CD8(+) T cells had lower cytokine expression than effector CD8(+) T cells, and protection against A2line19F was partial during the memory phase. We found that vaccineelicited effector antiRSV CD8(+) T cells protected mice against RSV infection and pathogenesis, and waning protection correlated with reduced CD8(+) T cell cytokine expression.