Poliovirus-specific CD4+ Th1 clones with both cytotoxic and helper activity mediate protective humoral immunity against a lethal poliovirus infection in transgenic mice expressing the human poliovirus receptor.
Poliovirus-specific CD4+ Th1 clones with both cytotoxic and helper activity mediate protective humoral immunity against a lethal poliovirus infection in transgenic mice expressing the human poliovirus receptor.
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DOI：
10.1084/jem.181.4.1285
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发表时间：
1995-04-01
期刊：
影响因子：
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通讯作者：
Mills KH
中科院分区：
文献类型：
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作者：
Mahon BP;Katrak K;Nomoto A;Macadam AJ;Minor PD;Mills KH
目前对CD4+辅助性T（Th）细胞在感染性疾病免疫中的功能的理解是分泌白细胞介素（IL）-2和干扰素-γ的Th1细胞诱导细胞免疫应答，而分泌IL-4、IL-5、IL-6和IL-10的Th2细胞为体液免疫提供辅助功能。我们使用了一组脊髓灰质炎病毒特异性小鼠CD4 + T细胞克隆和人脊髓灰质炎病毒受体转基因小鼠，以评估Th细胞亚群在脊髓灰质炎病毒保护性免疫中的作用。大多数T细胞克隆以及从脊髓灰质炎病毒感染或免疫的小鼠产生的多克隆T细胞分泌IL-2和干扰素-γ，但不分泌IL-4、IL-5或IL-10，这是Th1细胞的典型特征。Th1克隆显示针对特定脊髓灰质炎病毒肽脉冲靶细胞的主要组织相容性复合物II类限制性细胞毒性T淋巴细胞活性，但也为抗脊髓灰质炎病毒中和抗体产生提供帮助。为了研究体内免疫机制，我们在BALB/c（H-2d）背景下使用脊髓灰质炎病毒受体转基因小鼠。当用脊髓灰质炎病毒的强毒野生型菌株而不是减毒疫苗菌株进行静脉内攻击时，这些动物发展成脊髓灰质炎样疾病。此外，用疫苗株免疫的小鼠可保护其免受随后用野生型病毒的攻击。使用过继转移技术，我们证明了在存在多克隆脊髓灰质炎病毒特异性T细胞的情况下，有可能用致敏的B细胞提供保护，但当转基因小鼠单独接受B细胞或T细胞时，则无法提供保护。此外，当小鼠在VP 4特异性Th 1克隆存在的情况下接受致敏的B细胞时，观察到了保护作用。研究结果表明，Th1细胞可以通过体液免疫的辅助活性介导体内针对脊髓灰质炎病毒感染的保护性免疫应答，并且对内部脊髓灰质炎病毒衣壳蛋白VP4具有特异性的CD4 + T细胞可以为针对表面衣壳蛋白的保护性抗体应答提供有效帮助。
The current understanding of the function of CD4+ T helper (Th) cells in immunity to infectious diseases is that Th1 cells, which secrete interleukin (IL)-2 and interferon-gamma, induce cellular immune responses, whereas Th2 cells, which secrete IL-4, IL-5, IL-6, and IL- 10, provide helper function for humoral immunity. We have used a panel of poliovirus-specific murine CD4+ T cell clones and mice transgenic for the human poliovirus receptor to evaluate the role of Th cell subpopulations in protective immunity to poliovirus. The majority of T cell clones, as well as polyclonal T cells generated from mice infected or immunized with poliovirus, secreted IL-2 and interferon-gamma, but not IL-4, IL-5, or IL-10, a profile typical of Th1 cells. The Th1 clones displayed major histocompatibility complex class II-restricted cytotoxic T lymphocyte activity against specific poliovirus peptide- pulsed target cells, but also provided help for antipoliovirus neutralizing antibody production. To examine the mechanism of immunity in vivo, we have used poliovirus receptor-transgenic mice on a BALB/c (H-2d) background. These animals developed a poliomyelitis-like disease when challenged intravenously with a virulent wild-type strain of poliovirus, but not with an attenuated vaccine strain. Furthermore, mice immunized with the vaccine strain were protected against a subsequent challenge with wild-type virus. Using an adoptive transfer technique, we demonstrated that it was possible to confer protection with primed B cells in the presence of polyclonal poliovirus-specific T cells, but not when transgenic mice received either B cells or T cells alone. Furthermore, protection was observed when mice received primed B cells in the presence of a VP4-specific Th1 clone. The findings demonstrate that Th1 cells can mediate a protective immune response against poliovirus infection in vivo through helper activity for humoral immunity and that CD4+ T cells, specific for the internal poliovirus capsid protein, VP4, can provide effective help for a protective antibody response directed against surface capsid proteins.