Abstract
Peptide-induced peripheral T cell deletion leads to tolerance mediated by TRAIL-expressing CD8+ regulatory T cells (89.16)
The Journal of immunology (1950), Vol.182(1_Supplement), pp.89-89.16
04/01/2009
DOI: 10.4049/jimmunol.182.Supp.89.16
Abstract
Abstract Peripheral tolerance controls self-reactive T cells that escape thymic deletion. We previously showed that deletion of Ag-specific CD4+ T cells after soluble Ag injection leads to immune tolerance mediated by a CD8+ Treg population in response to the processing and presentation of the apoptotic T cells by the immune system. The CD8+ Treg maintain long-term tolerance to subsequent Ag challenge by deleting T cells that share the same Ag specificity. The present study explored the mechanism of action of these CD8+ Treg. Our data show OT-II T cells expand and contract equally in wildtype (WT) and TRAIL-/- mice after OVA323-339 injection. After contraction, WT mice were tolerant to subsequent OVA/CFA immunization, even when given fresh OT-II T cells, but TRAIL-/- mice displayed immunity. Analysis of the tolerant B6 mice found the transferred OT-II T cells did not undergo secondary expansion after OVA/CFA immunization, but secondary T cell expansion was evident in the non-tolerant TRAIL-/- mice. Subsequent investigation found direct killing of freshly transferred OT-II T cells in a TCR-specific manner in tolerant WT mice, but not in TRAIL-/- mice, and only CD8+ T cells from tolerant WT mice could transfer tolerance to naïve recipients. These data provide evidence for a novel mechanism of peripheral tolerance maintained through the cytotoxic activity of TRAIL-expressing CD8+ Treg against T cells of the same Ag specificity.
Details
- Title: Subtitle
- Peptide-induced peripheral T cell deletion leads to tolerance mediated by TRAIL-expressing CD8+ regulatory T cells (89.16)
- Creators
- Prajwal Gurung - University of IowaThomas A Ferguson - Washington University in St. LouisThomas S Griffith - University of Iowa
- Resource Type
- Abstract
- Publication Details
- The Journal of immunology (1950), Vol.182(1_Supplement), pp.89-89.16
- DOI
- 10.4049/jimmunol.182.Supp.89.16
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Language
- English
- Date published
- 04/01/2009
- Academic Unit
- Internal Medicine; Infectious Diseases
- Record Identifier
- 9984362752702771
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