Millennium Institute on Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago 8331010, Chile.
Departamento de Endocrinología, Escuela de Medicina, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago 8331010, Chile.
Viruses. 2020 Feb 20;12(2):233. doi: 10.3390/v12020233.
T cells play an essential role in the immune response against the human respiratory syncytial virus (hRSV). It has been described that both CD4 and CD8 T cells can contribute to the clearance of the virus during an infection. However, for some individuals, such an immune response can lead to an exacerbated and detrimental inflammatory response with high recruitment of neutrophils to the lungs. The receptor of most T cells is a heterodimer consisting of α and β chains (αβTCR) that upon antigen engagement induces the activation of these cells. The αβTCR molecule displays a broad sequence diversity that defines the T cell repertoire of an individual. In our laboratory, a recombinant Bacille Calmette-Guérin (BCG) vaccine expressing the nucleoprotein (N) of hRSV (rBCG-N-hRSV) was developed. Such a vaccine induces T cells with a Th1 polarized phenotype that promote the clearance of hRSV infection without causing inflammatory lung damage. Importantly, as part of this work, the T cell receptor (TCR) repertoire of T cells expanded after hRSV infection in naïve and rBCG-N-hRSV-immunized mice was characterized. A more diverse TCR repertoire was observed in the lungs from rBCG-N-hRSV-immunized as compared to unimmunized hRSV-infected mice, suggesting that vaccination with the recombinant rBCG-N-hRSV vaccine triggers the expansion of T cell populations that recognize more viral epitopes. Furthermore, differential expansion of certain TCRVβ chains was found for hRSV infection (TCRVβ8.3 and TCRVβ5.1,5.2) as compared to rBCG-N-hRSV vaccination (TCRVβ11 and TCRVβ12). Our findings contribute to better understanding the T cell response during hRSV infection, as well as the functioning of a vaccine that induces a protective T cell immunity against this virus.
T 细胞在针对人类呼吸道合胞病毒（hRSV）的免疫反应中发挥着至关重要的作用。已经描述过，CD4 和 CD8 T 细胞都可以在感染过程中帮助清除病毒。然而，对于某些人来说，这种免疫反应可能导致炎症反应加剧和有害，导致大量中性粒细胞招募到肺部。大多数 T 细胞的受体是由α和β链组成的异二聚体（αβTCR），抗原结合后诱导这些细胞的激活。αβTCR 分子显示出广泛的序列多样性，定义了个体的 T 细胞库。在我们的实验室中，开发了一种表达 hRSV 核蛋白（N）的重组卡介苗（BCG）疫苗（rBCG-N-hRSV）。这种疫苗诱导具有 Th1 极化表型的 T 细胞，促进 hRSV 感染的清除，而不会引起炎症性肺损伤。重要的是，作为这项工作的一部分，我们对未免疫的 hRSV 感染和 rBCG-N-hRSV 免疫的小鼠感染 hRSV 后 T 细胞扩增的 T 细胞受体（TCR）库进行了表征。与未免疫的 hRSV 感染小鼠相比，rBCG-N-hRSV 免疫小鼠肺部的 TCR 库更为多样化，这表明用重组 rBCG-N-hRSV 疫苗接种可触发识别更多病毒表位的 T 细胞群体的扩增。此外，与 rBCG-N-hRSV 疫苗接种（TCRVβ11 和 TCRVβ12）相比，发现 hRSV 感染时某些 TCRVβ 链的扩增存在差异（TCRVβ8.3 和 TCRVβ5.1、5.2）。我们的发现有助于更好地理解 hRSV 感染期间的 T 细胞反应，以及诱导针对这种病毒的保护性 T 细胞免疫的疫苗的作用。
