文章基本信息

标题：CD4+CD25−LAG3+ regulatory T cells controlled by the transcription factor Egr-2
本地全文：下载
作者：Tomohisa Okamura ; Keishi Fujio ; Mihoko Shibuya 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2009
卷号：106
期号：33
页码：13974-13979
DOI：10.1073/pnas.0906872106
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Regulatory T cells (Tregs) are engaged in the maintenance of immunological self-tolerance and immune homeostasis. IL-10 has an important role in maintaining the normal immune state. Here, we show that IL-10-secreting Tregs can be delineated in normal mice as CD4+CD25-Foxp3- T cells that express lymphocyte activation gene 3 (LAG-3), an MHC-class-II-binding CD4 homolog. Although {approx}2% of the CD4+CD25- T cell population consisted of CD4+CD25-LAG3+ T cells in the spleen, CD4+CD25-LAG3+ T cells are enriched to {approx}8% in the Peyer's patch. They are hypoproliferative upon in vitro antigenic stimulation and suppress in vivo development of colitis. Gene expression analysis reveals that CD4+CD25-LAG3+ Tregs characteristically express early growth response gene 2 (Egr-2), a key molecule for anergy induction. Retroviral gene transfer of Egr-2 converts naive CD4+ T cells into the IL-10-secreting and LAG-3-expressing phenotype, and Egr-2-transduced CD4+ T cells exhibit antigen-specific immunosuppressive capacity in vivo. Unlike Foxp3+ natural Tregs, high-affinity interactions with selecting peptide/MHC ligands expressed in the thymus do not induce the development of CD4+CD25-LAG3+ Tregs. In contrast, the number of CD4+CD25-LAG3+ Tregs is influenced by the presence of environmental microbiota. Thus, IL-10-secreting Egr-2+LAG3+CD4+ Tregs can be exploited for the control of peripheral immunity.
关键词：anergy ; Blimp-1 ; inflammatory bowel disease ; IL-10 ; type 1 regulatory T cells