TRAIL-expressing CD8+ T cells mediate tolerance following soluble peptide-induced peripheral T cell deletion

Prajwal Gurung; Tamara A Kucaba; Stephen P Schoenberger; Thomas A Ferguson; Thomas S Griffith

doi:10.1189/jlb.0610343

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TRAIL-expressing CD8+ T cells mediate tolerance following soluble peptide-induced peripheral T cell deletion

Journal article

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TRAIL-expressing CD8+ T cells mediate tolerance following soluble peptide-induced peripheral T cell deletion

Prajwal Gurung, Tamara A Kucaba, Stephen P Schoenberger, Thomas A Ferguson and Thomas S Griffith

Journal of leukocyte biology, Vol.88(6), pp.1217-1225

12/2010

DOI: 10.1189/jlb.0610343

PMCID: PMC2996898

PMID: 20807702

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Abstract

Mechanism behind transient peripheral tolerance induced after T cell deletion is identified as dependent on the cytotoxic activity of TRAIL-expressing CD8 + T reg . Peripheral tolerance controls the action of self-reactive T cells that escape thymic deletion. We showed previously that deletion of Ag-specific CD4 + T cells induced a CD8 + T reg population that maintained tolerance by deleting T cells with the same Ag specificity. The present study explored the mechanism of action of these CD8 + T reg . Following OT-II T cell deletion by soluble OVA 323–339 , B6 mice were unresponsive to challenge after CFA/OVA immunization, and Trail −/− or Dr5 −/− mice were immune, although all strains displayed similar OT-II peripheral deletion. Interestingly, B6 mice remained tolerant to OVA even after a second infusion of OT-II T cells. Tolerance could be transferred to naïve recipients using CD8 + T cells from B6 or Dr5 −/− mice that experienced peptide-induced peripheral OT-II deletion but not from Trail −/− mice. Subsequent investigation found that the mechanism of action of the CD8 + T reg was TRAIL-mediated OT-II T cell deletion in a TCR-specific manner. Furthermore, the tolerance was transient, as it was established by 14 days after peptide injection but lost by Day 56. Together, these data provide evidence to suggest that the mechanism behind transient peripheral tolerance induced following T cell deletion is the cytotoxic activity of TRAIL-expressing CD8 + T reg .

TCR-tg

Inflammation, Extracellular Mediators, & Effector Molecules

apoptosis

immunosuppression

Details

Title: Subtitle: TRAIL-expressing CD8+ T cells mediate tolerance following soluble peptide-induced peripheral T cell deletion
Creators: Prajwal Gurung - Department of Urology and
Tamara A Kucaba - Department of Urology and
Stephen P Schoenberger - La Jolla Institute for Allergy and Immunology, San Diego, California, USA; and
Thomas A Ferguson - Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, USA
Thomas S Griffith - Department of Urology and
Resource Type: Journal article
Publication Details: Journal of leukocyte biology, Vol.88(6), pp.1217-1225
DOI: 10.1189/jlb.0610343
PMID: 20807702
PMCID: PMC2996898
NLM abbreviation: J Leukoc Biol
ISSN: 0741-5400
eISSN: 1938-3673
Publisher: Society for Leukocyte Biology
Grant note: AI 077565; CA109446; CA81261; EY06765; EY015570; EY02687 / National Institutes of Health
Language: English
Date published: 12/2010
Academic Unit: Infectious Diseases; Internal Medicine
Record Identifier: 9984094324402771

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