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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell- and Tissue-Based Therapy*
  • Flow Cytometry
  • Graft Rejection / immunology
  • Graft Rejection / prevention & control*
  • Graft vs Host Disease / immunology
  • Graft vs Host Disease / prevention & control
  • Humans
  • Immune Tolerance / immunology*
  • Isoantigens / immunology*
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred BALB C
  • Skin Transplantation*
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / transplantation*
  • Transplantation Tolerance


  • Isoantigens