Department of Infectious Diseases, The Second Affiliated Hospital of Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi, China; Department of Epidemiology and Biostatistics, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Immunology. 2014 May;142(1):89-100. doi: 10.1111/imm.12235.
Human enterovirus 71 (EV71) is one of the major causes of hand, foot and mouth disease (HFMD), which leads to significant mortality in infected children. A prophylactic vaccine is urgently needed. However, little is known about the protective T-cell immunity in individuals infected with the EV71 virus. In this study, we performed a comprehensive ex vivo interferon-γ ELISPOT analysis in 31 children infected with EV71 as well as in 40 healthy adult controls of the CD4(+) and CD8(+) T-cell responses to overlapping peptides spanning the VP1 structural protein and RNA-dependent RNA polymerase (RdRp) non-structural protein. EV71-specific CD4 T-cell responses were detected in most of the acute patients and were mostly CD4-dependent RdRp-specific responses. CD8-dependent VP1 and RdRp-specific responses were also detected in a small proportion of recently infected children. There was no significant association between the strength of the T-cell responses and disease severity observed during the acute EV71 infection phase. Interestingly, an RdRp-specific, but no VP1-specific, CD4-dependent T-cell response was detected in 30% of the adult controls, and no T-cell responses were detected in healthy children. In addition, 24 individual peptides containing potential T-cell epitope regions were identified. The data suggest that CD4-dependent RdRp-specific T-cell responses may play an important role in protective immunity, and the epitopes identified in this study should provide valuable information for future therapeutic and prophylactic vaccine design as well as basic research.
肠道病毒 71 型（EV71）是手足口病（HFMD）的主要病原体之一，可导致感染儿童的死亡率显著升高。目前急需开发一种预防性疫苗。然而，对于感染 EV71 病毒的个体的保护性 T 细胞免疫反应，人们知之甚少。在这项研究中，我们对 31 名 EV71 感染患儿和 40 名健康成人对照者进行了全面的干扰素-γ ELISPOT 分析，以检测 CD4(+)和 CD8(+)T 细胞对 VP1 结构蛋白和 RNA 依赖性 RNA 聚合酶（RdRp）非结构蛋白重叠肽的反应。大多数急性患者均可检测到 EV71 特异性 CD4 T 细胞反应，且大多数为 CD4 依赖性 RdRp 特异性反应。一小部分近期感染的患儿也可检测到 CD8 依赖性 VP1 和 RdRp 特异性反应。在急性 EV71 感染期间，T 细胞反应的强度与疾病严重程度之间没有显著相关性。有趣的是，在 30%的成人对照组中检测到了一种 RdRp 特异性、但无 VP1 特异性的 CD4 依赖性 T 细胞反应，而在健康儿童中则未检测到 T 细胞反应。此外，还鉴定出了 24 个包含潜在 T 细胞表位区域的个体肽段。数据表明，CD4 依赖性 RdRp 特异性 T 细胞反应可能在保护性免疫中发挥重要作用，本研究中鉴定的表位应为未来的治疗性和预防性疫苗设计以及基础研究提供有价值的信息。
