Journal article
Systemic immunological tolerance to ocular antigens is mediated by TRAIL-expressing CD8+ T cells
The Journal of immunology (1950), Vol.186(2), pp.791-798
01/15/2011
DOI: 10.4049/jimmunol.1002678
PMCID: PMC3075597
PMID: 21169546
Abstract
Systemic immunological tolerance to Ag encountered in the eye restricts the formation of potentially damaging immune responses that would otherwise be initiated at other anatomical locations. We previously demonstrated that tolerance to Ag administered via the anterior chamber (AC) of the eye required Fas ligand-mediated apoptotic death of inflammatory cells that enter the eye in response to the antigenic challenge. Moreover, the systemic tolerance induced after AC injection of Ag was mediated by CD8(+) regulatory T cells. This study examined the mechanism by which these CD8(+) regulatory T cells mediate tolerance after AC injection of Ag. AC injection of Ag did not prime CD4(+) T cells and led to increased TRAIL expression by splenic CD8(+) T cells. Unlike wild-type mice, Trail(-/-) or Dr5(-/-) mice did not develop tolerance to Ag injected into the eye, even though responding lymphocytes underwent apoptosis in the AC of the eyes of these mice. CD8(+) T cells from Trail(-/-) mice that were first injected via the AC with Ag were unable to transfer tolerance to naive recipient wild-type mice, but CD8(+) T cells from AC-injected wild-type or Dr5(-/-) mice could transfer tolerance. Importantly, the transferred wild-type (Trail(+/+)) CD8(+) T cells were also able to decrease the number of infiltrating inflammatory cells into the eye; however, Trail(-/-) CD8(+) T cells were unable to limit the inflammatory cell ingress. Together, our data suggest that "helpless" CD8(+) regulatory T cells generated after AC injection of Ag enforce systemic tolerance in a TRAIL-dependent manner to inhibit inflammation in the eye.
Details
- Title: Subtitle
- Systemic immunological tolerance to ocular antigens is mediated by TRAIL-expressing CD8+ T cells
- Creators
- Thomas S Griffith - Department of Urology, University of Iowa, Iowa City, IA 52242, USA. thomas-griffith@uiowa.eduErik L BrincksPrajwal GurungTamara A KucabaThomas A Ferguson
- Resource Type
- Journal article
- Publication Details
- The Journal of immunology (1950), Vol.186(2), pp.791-798
- DOI
- 10.4049/jimmunol.1002678
- PMID
- 21169546
- PMCID
- PMC3075597
- NLM abbreviation
- J Immunol
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Grant note
- F32 EY006765 / NEI NIH HHS AI077565 / NIAID NIH HHS CA109446 / NCI NIH HHS R56 AI077565-01A1 / NIAID NIH HHS R01 EY006765 / NEI NIH HHS EY06765 / NEI NIH HHS R01 EY015570 / NEI NIH HHS R56 AI077565 / NIAID NIH HHS EY015570 / NEI NIH HHS R01 CA109446 / NCI NIH HHS
- Language
- English
- Date published
- 01/15/2011
- Academic Unit
- Infectious Diseases; Internal Medicine
- Record Identifier
- 9984094373002771
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