Skip to Main content Skip to Navigation
Journal articles

Combining Autologous Dendritic Cell Therapy with CD3 Antibodies Promotes Regulatory T Cells and Permanent Islet Allograft Acceptance

Abstract : Cell therapy and the use of mAbs that interfere with T cell effector functions constitute promising approaches for the control of allograft rejection. In the current study, we investigated a novel approach combining administration of autologous tolerogenic dendritic cells with short-term treatment with CD3-specific Abs. Permanent acceptance of pancreatic islet allografts was achieved in mice treated with the combination therapy the day before transplantation but not in recipients treated with either therapy alone. The combination treatment induced a marked decrease in T cells infiltrating the allografts and a sustained reduction of antidonor responses. Importantly, CD4+Foxp3+ regulatory T cells appeared to play a crucial role in the long-term graft acceptance. Their frequency increased significantly in the spleen, draining lymph nodes, and transplanted islets and remained elevated over the long term; they exhibited increased donor-specific suppressive functions; and their removal at the time of transplantation abrogated the therapeutic effect of the combined therapy. These results support the therapeutic potential of protocols combining autologous dendritic cells and low-dose CD3 Abs, both currently in clinical development, and that act in synergy to control allogeneic immune responses and favor graft survival in a full-mismatch situation.
Document type :
Journal articles
Complete list of metadatas

Cited literature [47 references]  Display  Hide  Download

https://www.hal.inserm.fr/inserm-02164449
Contributor : Sylvie Le Bihan <>
Submitted on : Tuesday, June 25, 2019 - 10:17:39 AM
Last modification on : Thursday, April 9, 2020 - 11:58:33 AM

File

 Restricted access
To satisfy the distribution rights of the publisher, the document is embargoed until : jamais

Please log in to resquest access to the document

Identifiers

Collections

Citation

Marije Baas, Chantal Kuhn, Fabrice Valette, Claire Mangez, Mercedes Segovia Duarte, et al.. Combining Autologous Dendritic Cell Therapy with CD3 Antibodies Promotes Regulatory T Cells and Permanent Islet Allograft Acceptance. Journal of Immunology, Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists, 2014, 193 (9), pp.4696-4703. ⟨10.4049/jimmunol.1401423⟩. ⟨inserm-02164449⟩

Share

Metrics

Record views

275