Program death-1 regulates peripheral T cell tolerance via an anergy-independent mechanism

Guilin Qiao; Lifen Yang; Zhenping Li; Haiyan Ying; Yassir Hassen; Fei Yin; Jian Zhang

doi:10.1016/j.clim.2012.02.006

Back

Program death-1 regulates peripheral T cell tolerance via an anergy-independent mechanism

Journal article

Open access

Peer reviewed

Program death-1 regulates peripheral T cell tolerance via an anergy-independent mechanism

Guilin Qiao, Lifen Yang, Zhenping Li, Haiyan Ying, Yassir Hassen, Fei Yin and Jian Zhang

Clinical immunology (Orlando, Fla.), Vol.143(2), pp.128-133

05/2012

DOI: 10.1016/j.clim.2012.02.006

PMCID: PMC3327760

PMID: 22459706

Files and links (1)

url

https://www.ncbi.nlm.nih.gov/pmc/articles/3327760View

Open Access

Abstract

Program death-1 (PD-1) has been documented to negatively regulate immune responses. However, the cellular and molecular mechanisms for PD-1-mediated immune suppression have not been fully elucidated. In this study, we show that loss of PD-1 does not lead to defective induction of CD4+ T cell anergy in vitro and in vivo. Rather, the absence of PD-1 inhibits the development of inducible CD4+Foxp3+ regulatory T cells (iTregs) induced by TGF-β in vitro. In support of this finding, PD-1 deficiency impairs the generation of iTregs in vivo and leads to development of severe T cell-transfer-induced colitis. Mechanistically, defective iTreg generation in the absence of PD-1 was attributed to the heightened phosphorylation of Akt. Therefore, we first demonstrate that PD-1 controls peripheral T cell tolerance via an anergy-independent but iTreg-dependent mechanism. ► Loss of PD-1 does not lead to defective induction of CD4+ T cell anergy. ► PD-1 deficiency facilitates the development of iTregs in vitro and in vivo. ► The facilitation of iTreg development by PD-1 seemed to be mediated by Akt.

Costimulation

T cell

Tolerance/suppression/anergy

Details

Title: Subtitle: Program death-1 regulates peripheral T cell tolerance via an anergy-independent mechanism
Creators: Guilin Qiao - Section of Nephrology, Department of Medicine, The University of Chicago, Chicago, IL 60637, USA
Lifen Yang - Section of Nephrology, Department of Medicine, The University of Chicago, Chicago, IL 60637, USA
Zhenping Li - Section of Nephrology, Department of Medicine, The University of Chicago, Chicago, IL 60637, USA
Haiyan Ying - Section of Nephrology, Department of Medicine, The University of Chicago, Chicago, IL 60637, USA
Yassir Hassen - Section of Nephrology, Department of Medicine, The University of Chicago, Chicago, IL 60637, USA
Fei Yin - Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China
Jian Zhang - Section of Nephrology, Department of Medicine, The University of Chicago, Chicago, IL 60637, USA
Resource Type: Journal article
Publication Details: Clinical immunology (Orlando, Fla.), Vol.143(2), pp.128-133
DOI: 10.1016/j.clim.2012.02.006
PMID: 22459706
PMCID: PMC3327760
NLM abbreviation: Clin Immunol
ISSN: 1521-6616
eISSN: 1521-7035
Publisher: Elsevier Inc
Grant note: DOI: 10.13039/501100002338, name: Ministry of Education of the People's Republic of China, award: [2007 3020; DOI: 10.13039/501100004543, name: China Scholarship Council; DOI: 10.13039/100000002, name: National Institutes of Health, award: R01 AI090901; DOI: 10.13039/100000968, name: American Heart Association, award: 09GRNT2010084
Language: English
Date published: 05/2012
Academic Unit: Pathology
Record Identifier: 9984046801002771

Metrics

22 Record Views

12 Times Cited - Web of Science