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Am J Transplant. 2013 Nov;13(11):3010-20. doi: 10.1111/ajt.12433. Epub 2013 Sep 18.

Clinical grade manufacturing of human alloantigen-reactive regulatory T cells for use in transplantation.

Author information

1
UCSF Diabetes Center, University of California, San Francisco, San Francisco, CA.

Abstract

Regulatory T cell (Treg) therapy has the potential to induce transplantation tolerance so that immunosuppression and associated morbidity can be minimized. Alloantigen-reactive Tregs (arTregs) are more effective at preventing graft rejection than polyclonally expanded Tregs (PolyTregs) in murine models. We have developed a manufacturing process to expand human arTregs in short-term cultures using good manufacturing practice-compliant reagents. This process uses CD40L-activated allogeneic B cells to selectively expand arTregs followed by polyclonal restimulation to increase yield. Tregs expanded 100- to 1600-fold were highly alloantigen reactive and expressed the phenotype of stable Tregs. The alloantigen-expanded Tregs had a diverse TCR repertoire. They were more potent than PolyTregs in vitro and more effective at controlling allograft injuries in vivo in a humanized mouse model.

KEYWORDS:

Cellular therapy; clinical application; regulatory T cells; tolerance induction

PMID:
24102808
PMCID:
PMC4161737
DOI:
10.1111/ajt.12433
[Indexed for MEDLINE]
Free PMC Article
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