T cell source of type 1 cytokines determines illness patterns in respiratory syncytial virus-infected mice.
T cell source of type 1 cytokines determines illness patterns in respiratory syncytial virus-infected mice.
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1 型细胞因子的 T 细胞来源决定了呼吸道合胞病毒感染小鼠的疾病模式。
DOI：
10.1172/jci119391
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
Graham,BS
中科院分区：
文献类型：
--
作者：
Tang,YW;Graham,BS
在接种疫苗时对细胞因子微环境的操纵可以影响对远程攻击的免疫应答，从而提供了在小鼠模型中研究呼吸道合胞病毒（RSV）疫苗增强疾病的分子发病机制的策略。尽管在福尔马林灭活RSV疫苗接种时用抗IL-4或重组IL-12（rIL-12）抗体处理诱导活病毒攻击后细胞因子mRNA表达模式的类似转变，但与rIL-12处理的小鼠相比，抗IL-4处理的小鼠具有增加的CD 8+细胞毒性T淋巴细胞活性和减少的疾病。为了确定导致这些模式的效应机制，在RSV攻击时，在体内选择性地耗尽CD 4+和/或CD 8 + T淋巴细胞。在rIL-12处理的小鼠中，CD 4+淋巴细胞对IFN-γ mRNA、RSV清除和疾病的贡献最大，而在抗IL-4处理的小鼠中，CD 8+淋巴细胞是主要效应子。负责病毒清除的效应子也介导疾病，表明病毒清除的效率决定疾病表达。这些结果表明，参与病毒攻击的免疫应答的效应细胞的表型可能是一个更重要的疾病的决定因素，而不是典型的分配给Th 1和Th 2淋巴细胞的细胞因子表达的模式。
Manipulation of the cytokine microenvironment at the time of vaccination can influence immune responses to remote challenge, providing a strategy to study the molecular pathogenesis of respiratory syncytial virus (RSV) vaccine-enhanced disease in the mouse model. Although treatment with antibody against IL-4 or recombinant IL-12 (rIL-12) at the time of formalin-inactivated RSV vaccination induced a similar shift in the pattern of cytokine mRNA expression upon live virus challenge, anti-IL-4 treated mice had increased CD8+ cytotoxic T lymphocyte activity and reduced illness compared with rIL-12-treated mice. To define effector mechanisms responsible for these patterns, CD4+ and/or CD8+ T lymphocytes were selectively depleted in vivo at the time of RSV challenge. In rIL-12-treated mice, CD4+ lymphocytes made the largest contribution to IFN-gamma mRNA, RSV clearance, and illness, while in anti-IL-4 treated mice, CD8+ lymphocytes were the major effector. The effector responsible for virus clearance also mediated illness, suggesting that efficiency of virus clearance determined disease expression. These results demonstrate that the phenotype of effector cells involved in the immune response to virus challenge may be a more important determinant of disease than patterns of cytokine expression classically assigned to Th1 and Th2 lymphocytes.