InBALB/c mice, IL-4 production during the initial phase of infection with Leishmania major is necessary and sufficient to instruct Th2 cell development resulting in progressive disease
InBALB/c mice, IL-4 production during the initial phase of infection with Leishmania major is necessary and sufficient to instruct Th2 cell development resulting in progressive disease
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DOI：
10.4049/jimmunol.164.9.4819
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发表时间：
2000-05-01
影响因子：
4.4
通讯作者：
Louis, JA
中科院分区：
文献类型：
--
作者：
Himmelrich, H;Launois, P;Louis, JA
与完整的BALB/c小鼠相反，V β 4（+）CD 4（+）T细胞缺陷的BALB/c小鼠对感染硕大利什曼原虫产生Th 1应答并具有抗性。V β 4缺陷型BALB/c小鼠在感染后1天内不能产生在BALB/c小鼠的V β 4 V α 8 CD 4（+）T细胞中发生的早期IL-4转录。在这里，我们证明了在感染后的第一个64小时内用IL-4治疗V β 4缺陷的BALB/c小鼠指示Th 2细胞发育和对感染的易感性。在感染前一天用抗CD 4 mAb处理的BALB/c小鼠中，IL-4不能逆转耐药表型，这表明IL-4的这些作用需要其与CD 4（+）T细胞的相互作用。与来自BALB/c小鼠的引流淋巴结细胞相反，来自V β 4缺陷BALB/c小鼠的细胞在感染后仍对IL-12有反应。引人注目的是，向V β 4缺陷型BALB/c小鼠施用IL-4通过下调IL-12 R β 2链表达而使其淋巴结细胞对IL-12无反应。本研究直接表明，在BALB/c小鼠中，IL-4是启动控制Th 2细胞成熟和对L.少校
contrast to intact BALB/c mice, BALB/c mice rendered deficient in V beta 4(+) CD4(+) T cells develop a Th1 response to infection with Leishmania major and are resistant. V beta 4-deficient BALB/c mice are unable to generate the early IL-4 transcription occurring in V beta 4 V alpha 8 CD4(+) T cells of BALB/c mice within 1 day of infection. Here we demonstrate that treatment of V beta 4-deficient BALB/c mice with IL-4 during the first 64 h after infection instructs Th2 cell development and susceptibility to infection. The demonstrated inability of IL-4 to reverse the resistant phenotype of BALB/c mice treated with anti-CD4 mAb the day before infection suggest that these effects of IL-4 require its interaction,vith CD4(+) T cells. In contrast to draining lymph node cells from BALB/c mice, cells from V beta 4-deficient BALB/c mice remain responsive to IL-12 following infection. Strikingly, administration of IL-4 to V beta 4-deficient BALB/c mice renders their lymph node cells unresponsive to IL-12 by down-regulating IL-12R beta 2-chain expression. This study directly demonstrates that in BALB/c mice IL-4 is necessary and sufficient to initiate the molecular events steering Th2 cell maturation and susceptibility to L. major.