IFN-γ- and IL-10-expressing virus epitopespecific Foxp3+ T reg cells in the central nervous system during encephalomyelitis

Jingxian Zhao; Jincun Zhao; Craig Fett; Kathryn Trandem; Erica Fleming; Stanley Perlman

doi:10.1084/jem.20110236

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IFN-γ- and IL-10-expressing virus epitopespecific Foxp3+ T reg cells in the central nervous system during encephalomyelitis

Journal article

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Peer reviewed

IFN-γ- and IL-10-expressing virus epitopespecific Foxp3+ T reg cells in the central nervous system during encephalomyelitis

Jingxian Zhao, Jincun Zhao, Craig Fett, Kathryn Trandem, Erica Fleming and Stanley Perlman

Journal of Experimental Medicine, Vol.208(8), pp.1571-1577

07/11/2011

DOI: 10.1084/jem.20110236

PMCID: PMC3149215

PMID: 21746812

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Abstract

Foxp3(+) CD4 regulatory T cells (T reg cells) are important in limiting immunopathology in infections. However, identifying pathogen-specific epitopes targeted by these cells has been elusive. Using MHC class II/peptide tetramers and intracellular cytokine staining, we identify T reg cells recognizing two virus-specific CD4 T cell epitopes in the coronavirus-infected central nervous system as well as naive T cell precursor pools. These T reg cells are detected at the same time as effector T cells (T eff cells) exhibiting the same specificity and can suppress T eff cell proliferation after stimulation with cognate peptide. These virus-specific T reg cells may be especially effective in inhibiting the immune response during the peak of infection, when virus antigen is maximal. Furthermore, these T reg cells express both IL-10 and IFN-γ after peptide stimulation. IFN-γ expression is maintained during both acute and chronic phases of infection. Identification of T reg cell target epitopes by cytokine production is also applicable in autoimmune disease because myelin oligodendrocyte glycoprotein-specific Foxp3(+) T reg cells express IL-10 and IL-17 at the peak of disease in mice with experimental autoimmune encephalomyelitis. These results show that pathogen epitope-specific Foxp3(+) T reg cells can be identified on the basis of cytokine production.

Immunology

Details

Title: Subtitle: IFN-γ- and IL-10-expressing virus epitopespecific Foxp3+ T reg cells in the central nervous system during encephalomyelitis
Creators: Jingxian Zhao
Jincun Zhao
Craig Fett
Kathryn Trandem
Erica Fleming
Stanley Perlman
Resource Type: Journal article
Publication Details: Journal of Experimental Medicine, Vol.208(8), pp.1571-1577
DOI: 10.1084/jem.20110236
PMID: 21746812
PMCID: PMC3149215
NLM abbreviation: J Exp Med
ISSN: 0022-1007
eISSN: 1540-9538
Language: English
Date published: 07/11/2011
Academic Unit: Microbiology and Immunology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Infectious Disease (Pediatrics)
Record Identifier: 9983777474802771

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