Dataset Information

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

ABSTRACT: 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 OVA₃₂₃₋₃₃₉, 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).

SUBMITTER: Gurung P

PROVIDER: S-EPMC2996898 | biostudies-other | 2010 Dec

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

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

Gurung Prajwal P Kucaba Tamara A TA Schoenberger Stephen P SP Ferguson Thomas A TA Griffith Thomas S TS

Journal of leukocyte biology 20100831 6

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 OVA₃₂₃₋₃₃₉, B6 mice were unresponsive to challenge after CFA/OVA immunization, and Trail⁻/⁻ or Dr5⁻/⁻ mice were immun ...[more]

PMID: 20807702

Similar Datasets

Project description:The maintenance of B cell homeostasis requires a tight control of B cell generation, survival, activation, and maturation. In lymphocytes upon activation, increased sensitivity to apoptotic signals helps controlling differentiation and proliferation. The death receptor Fas is important in this context because genetic Fas mutations in humans lead to an autoimmune lymphoproliferative syndrome that is similar to lymphoproliferation observed in Fas-deficient mice. In contrast, the physiological role of TNF-related apoptosis-inducing ligand receptors (TRAIL-Rs) in humans has been poorly studied so far. Indeed, most studies have focused on tumor cell lines and on mouse models whose results are difficult to transpose to primary human B cells. In the present work, the expression of apoptosis-inducing TRAIL-R1 and TRAIL-R2 and of the decoy receptors TRAIL-R3 and TRAIL-R4 was systematically studied in all developmental stages of peripheral B cells isolated from the blood and secondary lymphoid organs. Expression of TRAIL-Rs is modulated along development, with highest levels observed in germinal center B cells. In addition, T-dependent and T-independent signals elicited induction of TRAIL-Rs with distinct kinetics, which differed among B cell subpopulations: switched memory cells rapidly upregulated TRAIL-R1 and -2 upon activation while naïve B cells only reached similar expression levels at later time points in culture. Increased expression of TRAIL-R1 and -2 coincided with a caspase-3-dependent sensitivity to TRAIL-induced apoptosis in activated B cells but not in freshly isolated resting B cells. Finally, both TRAIL-R1 and TRAIL-R2 could signal actively and both contributed to TRAIL-induced apoptosis. In conclusion, this study provides a systematic analysis of the expression of TRAIL-Rs in human primary B cells and of their capacity to signal and induce apoptosis. This dataset forms a basis to further study and understand the dysregulation of TRAIL-Rs and TRAIL expression observed in autoimmune diseases. Additionally, it will be important to foresee potential bystander immunomodulation when TRAIL-R agonists are used in cancer treatment.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets