Central role for interleukin-4 in regulating nitric oxide-mediated inhibition of T-cell proliferation and gamma interferon production in schistosomiasis
Central role for interleukin-4 in regulating nitric oxide-mediated inhibition of T-cell proliferation and gamma interferon production in schistosomiasis
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DOI：
10.1128/iai.70.1.177-184.2002
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发表时间：
2002-01-01
影响因子：
3.1
通讯作者：
Pearce, EJ
中科院分区：
文献类型：
--
作者：
Patton, EA;La Flamme, AC;Pearce, EJ
曼氏血吸虫感染的野生型（WT）小鼠产生Th 2应答和慢性疾病。相比之下，感染的白细胞介素-4双缺陷（IL-4（-/-））小鼠会出现Th 1样反应和急性致命综合征。这些动物中的疾病严重程度与一氧化氮（NO）的过度和延长的产生相关，所述一氧化氮（NO）的产生与在不存在IL-4的情况下增强的抗原驱动的γ干扰素（IFN-γ）产生相关。引人注目的是，感染的IL-4（-/-）小鼠的脾淋巴细胞在体外用抗原或抗CD 3抗体刺激后不能增殖，也不能像感染的WT小鼠的脾淋巴细胞一样增殖。与抗原驱动的IFN-γ应答相反，脾细胞的抗CD 3抗体刺激导致来自感染的IL-4（-/-）小鼠的CD 8细胞产生的IFN-γ显著少于来自感染的WT小鼠或正常小鼠的那些。NO在很大程度上是导致感染的IL-4（-/-）小鼠中T细胞功能受损的原因，因为iNOS的抑制显著增强增殖和IFN-γ产生。
Schistosoma mansoni-infected wild-type (WT) mice develop a Th2 response and chronic disease. In contrast, infected interleukin-4 double-deficient (IL-4(-/-)) mice develop a Th1-like response and an acute, lethal syndrome. Disease severity in these animals correlates with excessive and prolonged production of nitric oxide (NO) associated with enhanced antigen-driven gamma interferon (IFN-gamma) production in the absence of IL-4. Strikingly, splenic lymphocytes from infected IL-4(-/-) mice failed to proliferate as well as those from infected WT mice following stimulation in vitro with antigen or anti-CD3 antibody. Contrary to antigen-driven IFN-gamma responses, anti-CD3 antibody stimulation of splenocytes resulted in significantly less IFN-gamma being produced by CD8 cells from infected IL-4(-/-) mice than by those from infected WT mice or normal mice. NO is largely responsible for the impaired T-cell functions in infected IL-4(-/-) mice, as inhibition of iNOS significantly enhanced proliferation and IFN-gamma production.