ϟ
 
DOI: 10.4049/jimmunol.1201090
¤ OpenAccess: Bronze
This work has “Bronze” OA status. This means it is free to read on the publisher landing page, but without any identifiable license.

A Converse 4-1BB and CD40 Ligand Expression Pattern Delineates Activated Regulatory T Cells (Treg) and Conventional T Cells Enabling Direct Isolation of Alloantigen-Reactive Natural Foxp3+ Treg

Anne Schoenbrunn,Marco Frentsch,Siegfried Köhler,Jacqueline Keye,Hans Dooms,Beate Moewes,Jun Dong,Christoph Loddenkemper,Joachim Sieper,Peng Wu,Chiara Romagnani,Nadine Matzmohr,Andreas Thiel

Treg cell
FOXP3
Biology
2012
Abstract Natural regulatory T cells (nTreg) play a central role in the induction and maintenance of immunological tolerance. Experimental transplant models and recent clinical trials demonstrate that nTreg can control alloreactivity. To upgrade Treg-based cell therapies to a selective suppression of undesired immune reactions, only the transfer of Ag-specific nTreg represents the appropriate therapeutic option. However, Ag-specific nTreg are present at extremely low frequencies in the periphery, and so far appropriate surface markers for their precise identification are missing. In this study, we demonstrate that activated nTreg and activated conventional T cells differ in their 4-1BB and CD40 ligand (CD40L) expression signatures, allowing a clear dissection from each other. Based on the expression of 4-1BB and absence of CD40L expression, human alloantigen-reactive Foxp3+ nTreg can be directly isolated from MLR cultures with high purity. Alloantigen-reactive 4-1BB+CD40L− nTreg were characterized by a completely demethylated Treg-specific demethylated region and showed alloantigen-specific suppressive properties superior to polyclonal Treg. Importantly, isolated 4-1BB+CD40L− nTreg maintain the nTreg phenotype and alloantigen-reactivity after in vitro expansion. Our results offer the possibility to simultaneously analyze Ag-specific nTreg and conventional T cells, and to establish cellular therapies with Ag-specific nTreg aiming at a specific inhibition of unwanted immunity.
Loading...
    Cite this:
Generate Citation
Powered by Citationsy*
    A Converse 4-1BB and CD40 Ligand Expression Pattern Delineates Activated Regulatory T Cells (Treg) and Conventional T Cells Enabling Direct Isolation of Alloantigen-Reactive Natural Foxp3+ Treg” is a paper by Anne Schoenbrunn Marco Frentsch Siegfried Köhler Jacqueline Keye Hans Dooms Beate Moewes Jun Dong Christoph Loddenkemper Joachim Sieper Peng Wu Chiara Romagnani Nadine Matzmohr Andreas Thiel published in 2012. It has an Open Access status of “bronze”. You can read and download a PDF Full Text of this paper here.