Millennium Nucleus on Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Alameda 340, Santiago, Chile.
J Immunol. 2010 Dec 15;185(12):7633-45. doi: 10.4049/jimmunol.0903452. Epub 2010 Nov 17.
Infection by the respiratory syncytial virus (RSV) can cause extensive inflammation and lung damage in susceptible hosts due to a Th2-biased immune response. Such a deleterious inflammatory response can be enhanced by immunization with formalin- or UV-inactivated RSV, as well as with vaccinia virus expressing the RSV-G protein. Recently, we have shown that vaccination with rBCG-expressing RSV Ags can prevent the disease in the mouse. To further understand the immunological mechanisms responsible for protection against RSV, we have characterized the T cell populations contributing to virus clearance in mice immunized with this BCG-based vaccine. We found that both CD4(+) and CD8(+) T cells were recruited significantly earlier to the lungs of infected mice that were previously vaccinated. Furthermore, we observed that simultaneous adoptive transfer of CD8(+) and CD4(+) RSV-specific T cells from vaccinated mice was required to confer protection against virus infection in naive recipients. In addition, CD4(+) T cells induced by vaccination released IFN-γ after RSV challenge, indicating that protection is mediated by a Th1 immune response. These data suggest that vaccination with rBCG-expressing RSV Ags can induce a specific effector/memory Th1 immune response consisting on CD4(+) and CD8(+) T cells, both necessary for a fully protective response against RSV. These results support the notion that an effective induction of Th1 T cell immunity against RSV during childhood could counteract the unbalanced Th2-like immune response triggered by the natural RSV infection.
呼吸道合胞病毒（RSV）感染可导致易感宿主产生 2 型免疫反应偏向的广泛炎症和肺损伤。由于福尔马林或紫外线灭活的 RSV 以及表达 RSV-G 蛋白的牛痘病毒的免疫接种，这种有害的炎症反应会增强。最近，我们已经表明，用表达 RSV Ag 的 rBCG 进行免疫接种可以预防小鼠疾病。为了进一步了解针对 RSV 的保护性免疫机制，我们已经对用这种基于 BCG 的疫苗免疫接种的小鼠清除病毒的 T 细胞群进行了特征描述。我们发现，在先前接种过疫苗的感染小鼠的肺部中，CD4(+)和 CD8(+) T 细胞均明显更早地被募集。此外，我们观察到，来自接种疫苗的小鼠的 CD8(+)和 CD4(+) RSV 特异性 T 细胞的同时过继转移对于在未感染的受者中赋予对病毒感染的保护是必需的。此外，接种疫苗诱导的 CD4(+) T 细胞在 RSV 攻击后释放 IFN-γ，表明保护是由 Th1 免疫反应介导的。这些数据表明，用表达 RSV Ag 的 rBCG 进行免疫接种可以诱导针对 RSV 的特异性效应/记忆 Th1 免疫反应，由 CD4(+)和 CD8(+) T 细胞组成，两者都是针对 RSV 完全保护性反应所必需的。这些结果支持这样的观点，即针对 RSV 的 Th1 T 细胞免疫的有效诱导在儿童时期可能会抵消由天然 RSV 感染引发的不平衡 2 型样免疫反应。
