Cutting edge: Human eosinophils regulate T cell subset selection through indoleamine 2,3-dioxygenase
Cutting edge: Human eosinophils regulate T cell subset selection through indoleamine 2,3-dioxygenase
复制标题
DOI：
10.4049/jimmunol.173.10.5909
复制
发表时间：
2004-11-15
影响因子：
4.4
通讯作者：
Moqbel, R
中科院分区：
文献类型：
--
作者：
Odemuyiwa, SO;Ghahary, A;Moqbel, R
过敏包括嗜酸性粒细胞增多和Th2极化。吲哚胺2,3-双加氧酶（IDO）催化色氨酸转化为犬尿氨酸（KYN）调节T细胞功能。我们发现人类嗜酸性细胞组成性地表达IDO。ifn - γ处理的嗜酸性粒细胞在4小时内IDO mRNA增加了8倍，IL-3、IL-5和GM-CSF对基线IDO表达没有影响。IL-3预处理嗜酸性粒细胞使ifn - γ诱导的IDO mRNA表达低于基线。相反，GM-CSF，而不是IL-5，导致ifn - γ诱导的IDO增加2倍。单独用IL-3、IL-5、GM-CSF或ifn - γ处理表达IDO酶活性（培养48小时后上清中存在KYN）。CD28交联导致培养上清中可测量的KYN，被中和的抗ifn - γ抑制。嗜酸性粒细胞与产生ifn - γ的T细胞系共培养，而不是与产生il -4的T细胞系共培养，导致细胞凋亡并抑制CD3或cd31cd28诱导的增殖。嗜酸性粒细胞浸润哮喘肺和相关淋巴组织表现出细胞内IDO免疫反应性。因此，嗜酸性粒细胞可能通过IDO维持Th2偏倚。
Allergy involves eosinophilia and Th2 polarization. Indoleamine 2,3-dioxygenase (IDO)-catalyzed conversion of tryptophan to kynurenines (KYN) regulates T cell function. We show that human eosinophils constitutively express IDO. Eosinophils treated with IFN-gamma showed an 8-fold increase in IDO mRNA within 4 h, IL-3, IL-5, and GM-CSF had no effect on baseline IDO expression. IL-3 pretreatment of eosinophils reduced IFN-gamma-induced IDO mRNA expression below baseline. Conversely, GM-CSF, but not IL-5, resulted in a 2-fold increase in IFN-gamma-induced IDO. Treatment with IL-3, IL-5, GM-CSF, or IFN-gamma alone expressed IDO enzymatic activity (the presence of KYN in supernatants 48 h postculture). CD28 cross-linking resulted in measurable KYN in culture supernatants, inhibitable by a neutralizing anti-IFN-gamma. Coculture of eosinophils with an IFN-gamma-producing T cell line, hut not IL-4-producing T cell clone, led to apoptosis and inhibition of CD3 or CD31CD28-induced proliferation. Eosinophils infiltrating asthmatic lung and associated lymphoid tissue exhibited intracellular IDO immunoreactivity. Eosinophils may, therefore, maintain Th2 bias through IDO.