OX40 Ligation on activated T cells enhances the control of Cryptococcus neoformans and reduces pulmonary eosinophilia
OX40 Ligation on activated T cells enhances the control of Cryptococcus neoformans and reduces pulmonary eosinophilia
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DOI：
10.4049/jimmunol.170.12.6125
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发表时间：
2003-06-15
影响因子：
4.4
通讯作者：
Hussell, T
中科院分区：
文献类型：
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作者：
Humphreys, IR;Edwards, L;Hussell, T
新型隐球菌感染后C57BL/6小鼠肺嗜酸性粒细胞增多是由CD4+ Th2细胞驱动的。防止嗜酸性粒细胞增多的免疫学机制尚不完全清楚。OX40 （CD134）与其配体OX40L的相互作用与T细胞活化和细胞迁移有关。与CD28不同，OX40仅在Ag激活后1-2天在T细胞上表达。因此，对这一途径的操作将针对最近激活的T细胞，而不影响初始库。在这项研究中，我们发现OX40与OX40L:Ig融合蛋白的结合可驱动CD4+ T细胞产生ifn - γ，并减少肺中嗜酸性粒细胞和新生梭菌的负担。使用基因缺失小鼠，我们发现嗜酸性粒细胞和病原体负担的减少需要IL-12和/或ifn - γ。新生C.虫感染本身仅部分诱导apc表达OX40L。提供外源性OX40L揭示了该途径在预防C线虫诱导的嗜酸性粒细胞增多中的关键作用。
Pulmonary eosinophilia induced in C57BL/6 mice after Cryptococcus neoformans infection is driven by CD4+ Th2 cells. The immunological mechanisms that protect against eosinophilia are not fully understood. Interaction of OX40 (CD134) and its ligand, OX40L, has been implicated in T cell activation and cell migration. Unlike CD28, OX40 is only expressed on T cells 1-2 days after Ag activation. Manipulation of this pathway would therefore target recently activated T cells, leaving the naive repertoire unaffected. In this study, we show that engagement of OX40 by an OX40L:Ig fusion protein drives IFN-gamma production by CD4+ T cells and reduces eosinophilia and C. neoformans burden in the lung. Using gene-depleted mice, we show that reduction of eosinophilia and pathogen burden requires IL-12 and/or IFN-gamma. C. neoformans infection itself only partially induces OX40L expression by APCs. Provision of exogenous OX40L reveals a critical role of this pathway in the prevention of C neaformans-induced eosinophilia.