Identification of a novel subset of human circulating memory CD4+ T cells that produce both IL-17A and IL-4
Identification of a novel subset of human circulating memory CD4+ T cells that produce both IL-17A and IL-4
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DOI：
10.1016/j.jaci.2009.10.012
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发表时间：
2010-01-01
影响因子：
14.2
通讯作者：
Annunziato, Francesco
中科院分区：
文献类型：
--
作者：
Cosmi, Lorenzo;Maggi, Laura;Annunziato, Francesco
工作背景：目的：研究人IL-17 A分泌型CD 4（+）T-H细胞（T（H）17）与IL-4分泌型CD 4（+）T-H细胞（T（H）2）的关系。从人循环CD 4（+）T细胞的CCR 6（+）CD 161（+）部分产生的T细胞克隆，其包含几乎所有的T（H）17细胞，以及来自健康受试者和哮喘患者的循环CD 4（+）T细胞，通过流式细胞术评估其细胞因子产生谱。一小部分CCR 6（+）CD 161（+）CD 4（+）T细胞克隆显示出产生IL-17 A和IL-4（T（H）17/T（H）12）的能力。T（H）17/T（H）2克隆也产生IL-5、IL-8、IL-9、IL-13、IL-21和IL-22，并显示出诱导IgE体外分泌的能力。正常人外周血CD 4（+）T细胞中T（H）17/T（H）12细胞的比例很低，而慢性哮喘患者外周血T细胞中T（H）17/T（H）12细胞的比例明显增高。TT（H）17/T（H）2细胞在任何实验条件下都不能从幼稚脐血CD 4（+）T细胞中获得。然而，当在适当的极化条件下克隆循环记忆性CCR 6（+）CD 161（+）CD 4（+）T细胞时，T（H）17/T（H）2克隆起源于IL-4的存在，这表明富含IL-4的微环境可以诱导记忆性T（H）17细胞向T（H）17/T（H）2细胞的转变。由于其独特的功能特性和支气管哮喘患者循环中数量的增加，这种以前未知的T（H）17/T（H）2细胞群可能在这种疾病的发病机制中发挥一定作用。（J Allergy Clin Immunol 2010;125：222-230.）
Background: IL-17A has been suggested to play a pathogenic role in bronchial asthma and other allergic disorders.Objective: Study of the relationship between human IL-17A-producing CD4(+) T-H cells (T(H)17) and IL-4-producing CD4(+) T-H (T(H)2) cells.Methods: T-cell clones generated from the CCR6(+)CD161(+) fraction of human circulating CD4(+) T cells, which contains virtually all T(H)17 cells, as well as circulating CD4(+) T cells from both healthy subjects and patients with asthma, were assessed by flow cytometry for their cytokine production profile.Results: A small proportion of CCR6(+)CD161(+)CD4(+) T-cell clones showed the ability to produce both IL-17A and IL-4 (T(H)17/T(H)12). T(H)17/T(H)2 clones also produced IL-5, IL-8, IL-9, IL-13, IL-21, and IL-22 and displayed the ability to induce the in vitro secretion of IgE. A very few T(H)17/T(H)12 cells were found among circulating CD4(+) T cells from normal subjects, but their proportions were significantly increased in the circulation of patients with chronic asthma. TT(H)17/T(H)2 cells could not be derived from naive umbilical cord blood CD4(+) T cells under any experimental condition. However, when circulating memory CCR6(+)CD161(+)CD4(+) T cells were cloned under appropriate polarizing conditions, T(H)17/T(H)2 clones originated in the presence of IL-4, suggesting that an IL-4-rich microenvironment may induce the shifting of memory T(H)17 cells into T(H)17/T(H)2 cells.Conclusion: Because of its peculiar functional properties and the increased numbers in the circulation of patients with bronchial asthma, this previously unknown population of T(H)17/T(H)2 cells may play some role in the pathogenesis of this disease. (J Allergy Clin Immunol 2010;125:222-230.)