Tissue-level regulation of Th1 and Th2 primary and memory CD4 T cells in response to Listeria infection
Tissue-level regulation of Th1 and Th2 primary and memory CD4 T cells in response to Listeria infection
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DOI：
10.4049/jimmunol.168.9.4504
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发表时间：
2002-05-01
影响因子：
4.4
通讯作者：
Lefrançois, L
中科院分区：
文献类型：
--
作者：
Marzo, AL;Vezys, V;Lefrançois, L
Ag特异性Th 1和Th 2产生亮氨酸的CD 4 T细胞在次级淋巴和三级组织中进行定量，口服单核细胞增生李斯特菌感染。虽然以前认为对李斯特菌的应答主要是Th 1样的，但产生IL-4或IL-5的CD 4 T细胞占总体初级和记忆应答的相当大的比例。与脾和淋巴结相比，肺、肝和肠固有层（LP）中产生IFN-γ、IL-4或IL-5的初级效应或记忆CD 4 T细胞的频率显著较高。然而，IL-4-和IL-5-产生细胞的最大数量检测在LP数天后的Th 1反应的峰值，IL-5的生产偏向于粘膜组织。值得注意的是，回忆反应导致持续的Th 1和Th 2反应在三级，但不是淋巴组织和长期保留的Th 1和Th 2记忆细胞在LP中的比例相等。最后，CD 40配体对于脾和LP中IFN-γ的诱导是必需的，但在肝和肺中不是必需的，而IL-4应答仅需要脾中的CD 40配体。因此，控制效应表型的规则和CD 4应答的总体幅度在个体组织水平上受到调节。
Ag-specific Th1 and Th2 cytokine-producing CD4 T cells were quantitated in secondary lymphoid and tertiary tissues following oral Listeria monocytogenes infection. Although the response to Listeria was previously believed to be predominately Th1 like, CD4 T cells producing IL-4 or IL-5 comprised a substantial proportion of the overall primary and memory response. The frequency of IFN-gamma-, IL-4-, or IL-5-producing primary effector or memory CD4 T cells was significantly higher in lung, liver, and intestinal lamina propria (LP) as compared with spleen and lymph node. However, maximum numbers of IL-4- and IL-5-producing cells were detected in the LP several days after the peak of the Th1 response, and IL-5 production was skewed toward the mucosal tissues. Remarkably, the recall response resulted in sustained Th1 and Th2 responses in tertiary, but not lymphoid tissues and long-term retention of Th1 and Th2 memory cells in equal proportions in the LP. Finally, CD40 ligand was essential for induction of IFN-gamma in the spleen and LP, but not in the liver and lung, while the IL-4 response required CD40 ligand only in the spleen. Therefore, the rules governing the effector phenotype, and the overall magnitude of the CD4 response, are regulated at the level of individual tissues.