Natural Tr1-like cells do not confer long-term tolerogenic memory

Author:

Yadava Koshika12ORCID,Medina Carlos Obed1ORCID,Ishak Heather1,Gurevich Irina1,Kuipers Hedwich13,Shamskhou Elya Ali1,Koliesnik Ievgen O1,Moon James J45ORCID,Weaver Casey6,Nadeau Kari Christine7,Bollyky Paul L1ORCID

Affiliation:

1. Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Beckman Center, Stanford University School of Medicine, Stanford, United States

2. Radcliffe Department of Medicine, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom

3. Department of Clinical Neurosciences, University of Calgary, Calgary, Canada

4. Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Charlestown, United States

5. Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Harvard Medical School, Charlestown, United States

6. Bevill Biomedical Research Building, The University of Alabama at Birmingham, Birmingham, United States

7. Sean N Parker Center for Allergy & Asthma Research, Stanford University, Mountain View, United States

Abstract

IL-10-producing Tr1 cells promote tolerance but their contributions to tolerogenic memory are unclear. Using 10BiT mice that carry a Foxp3-eGFP reporter and stably express CD90.1 following IL-10 production, we characterized the spatiotemporal dynamics of Tr1 cells in a house dust mite model of allergic airway inflammation. CD90.1+Foxp3-IL-10+ Tr1 cells arise from memory cells and rejoin the tissue-resident memory T-cell pool after cessation of IL-10 production. Persistent antigenic stimulation is necessary to sustain IL-10 production and Irf1 and Batf expression distinguishes CD90.1+Foxp3-IL-10+ Tr1 cells from CD90.1+Foxp3-IL-10- ‘former’ Tr1. Depletion of Tr1-like cells after primary sensitization exacerbates allergic airway inflammation. However, neither transfer nor depletion of former Tr1 cells influences either Tr1 numbers or the inflammatory response during subsequent allergen memory re-challenge weeks later. Together these data suggest that naturally-arising Tr1 cells do not necessarily give rise to more Tr1 upon allergen re-challenge or contribute to tolerogenic memory. This phenotypic instability may limit efforts to re-establish tolerance by expanding Tr1 in vivo.

Funder

National Institutes of Health

Swiss National Science Foundation

Child Health Research Institute Stanford

Ford Foundation

Stanford University

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

Cited by 8 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3