ROLE OF LYMPHOCYTE-T SUBSETS IN THE PATHOGENESIS OF PRIMARY INFECTION AND RECHALLENGE WITH RESPIRATORY SYNCYTIAL VIRUS IN MICE
ROLE OF LYMPHOCYTE-T SUBSETS IN THE PATHOGENESIS OF PRIMARY INFECTION AND RECHALLENGE WITH RESPIRATORY SYNCYTIAL VIRUS IN MICE
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DOI：
10.1172/jci115362
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发表时间：
1991-09-01
影响因子：
15.9
通讯作者：
KARZON, DT
中科院分区：
文献类型：
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作者：
GRAHAM, BS;BUNTON, LA;KARZON, DT
使用 BALB/c 小鼠模型研究了 CD4+ 和 CD8+ T 淋巴细胞在终止呼吸道合胞病毒 (RSV) 复制、引起疾病和防止再感染中的作用，其中通过注射针对相应小鼠淋巴细胞决定簇的 Mab 来耗尽 CD4+ 或 CD8+ 淋巴细胞或两者。 在初次感染和再次攻击后评估 RSV 复制、疾病和病理学的动力学。 CD4+ 和 CD8+ 淋巴细胞亚群均参与初次感染后 RSV 复制的终止。 当两个T淋巴细胞亚群都被耗尽时，RSV复制显着延长，但没有明显的疾病，这表明宿主免疫反应而不是病毒杀细胞作用是小鼠疾病的主要决定因素。 尽管 CD8+ 淋巴细胞似乎在这一特定系统中发挥着主导作用，但 CD4+ 和 CD8+ 淋巴细胞都会导致疾病。 组织学反应分析表明，正常小鼠在再次给药后出现支气管血管周围淋巴细胞聚集体需要 CD4+ 淋巴细胞，并且肺泡淋巴细胞的存在与疾病相关。 据推测，抗体是保护小鼠免受 RSV 感染的疾病预防机制，而 T 淋巴细胞是疾病的重要决定因素。 进一步描述RSV在初次感染和再感染中诱导的免疫发病机制将为疫苗策略的开发提供重要信息。
The role of CD4+ and CD8+ T lymphocytes in terminating respiratory syncytial virus (RSV) replication, causing disease, and protecting from reinfection was investigated using a BALB/c mouse model in which CD4+ or CD8+ lymphocytes or both were depleted by injections of Mab directed against the respective mouse lymphocyte determinants. Kinetics of RSV replication, illness, and pathology were assessed after primary infection and rechallenge. Both CD4+ and CD8+ lymphocyte subsets were involved in terminating RSV replication after primary infection. When both T lymphocyte subsets were depleted RSV replication was markedly prolonged, yet no illness was evident, suggesting that host immune response rather than viral cytocidal effect was the primary determinant of disease in mice. Both CD4+ and CD8+ lymphocytes contributed to illness, although CD8+ lymphocytes appeared to play the dominant role in this particular system. Analysis of histological responses suggested that CD4+ lymphocytes were required for the appearance of peribronchovascular lymphocytic aggregates seen in normal mice after rechallenge, and that the presence of alveolar lymphocytes was correlated with illness. It is postulated that antibody is an illness-sparing mechanism for protecting mice from RSV infection, and that T lymphocytes are an important determinant of illness. Further delineation of RSV-induced immunopathogenesis in primary infection and reinfection will provide important information for the development of vaccine strategies.