ANTI-IL-4 TREATMENT AT IMMUNIZATION MODULATES CYTOKINE EXPRESSION, REDUCES ILLNESS, AND INCREASES CYTOTOXIC T-LYMPHOCYTE ACTIVITY IN MICE CHALLENGED WITH RESPIRATORY SYNCYTIAL VIRUS
ANTI-IL-4 TREATMENT AT IMMUNIZATION MODULATES CYTOKINE EXPRESSION, REDUCES ILLNESS, AND INCREASES CYTOTOXIC T-LYMPHOCYTE ACTIVITY IN MICE CHALLENGED WITH RESPIRATORY SYNCYTIAL VIRUS
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DOI：
10.1172/jci117546
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发表时间：
1994-11-01
影响因子：
15.9
通讯作者：
GRAHAM, BS
中科院分区：
文献类型：
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作者：
TANG, YW;GRAHAM, BS
在呼吸道合胞病毒（RSV）攻击时，先前肌肉注射灭活全病毒免疫的小鼠表现出类似Th2型的细胞因子mRNA模式，而鼻内接种活病毒免疫的小鼠则表现出类似Th1型的模式。在本研究中，我们评估了抗白细胞介素 - 4（IL - 4）治疗对免疫后免疫应答诱导的影响。在接种灭活RSV时用抗IL - 4处理的小鼠在活病毒攻击后临床疾病减轻，这通过体重减轻、疾病评分和病毒复制来衡量。这与增强的CD8 + 细胞毒性T淋巴细胞（CTL）活性、相对于IL - 4 mRNA干扰素 - γ（IFN - γ）mRNA表达增加以及在攻击前抗IL - 4处理的小鼠中RSV特异性IgG(2a)滴度更高有关。在攻击时给予抗IL - 4对疾病、免疫球蛋白同种型或细胞因子模式没有影响。这些结果表明，在免疫时抑制IL - 4的作用可使淋巴细胞的选择性激活转变为更类似Th1型的反应。这种细胞因子环境与增强的CTL活性相关，这可能是在后续RSV攻击时病毒快速清除和疾病减轻的原因。
Upon respiratory syncytial virus (RSV) challenge, mice previously immunized intramuscularly with inactivated whole virus express a Th2-like pattern of cytokine mRNA, while mice immunized with live virus intranasally express a Th1-like pattern. In this study, we evaluated the effects of anti-IL-4 treatment on the induction of immune responses after immunization. Mice treated with anti-IL-4 at the time of immunization with inactivated RSV had reduced clinical illness after live virus challenge, as measured by weight loss, illness score, and virus replication. This was associated with an augmented CD8+ cytotoxic T lymphocyte (CTL) activity, increased expression of IFN-gamma mRNA relative to IL-4 mRNA, and a higher titer of RSV-specific IgG(2a) in the antin-4 treated mice before challenge. Anti-IL-4 administration at the time of challenge had no effects on illness, immunoglobulin isotype, or cytokine patterns. These results suggest that inhibition of IL-4 action at immunization can shift the selective activation of lymphocytes to a more Th1-like response. This cytokine milieu is associated with augmented CTL activity, which may be the factor responsible for rapid viral clearance and reduced illness at the time of remote RSV challenge.