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Redirecting human CD4+CD25+ regulatory T cells from the peripheral blood with pre-defined target specificity

Gene Therapy volume 16, pages 1088–1096 (2009)Cite this article

Abstract

Recent insight into the balance of self-tolerance and auto-aggression has raised interest in using human regulatory T (Treg) cells for adoptive immunotherapy of unlimited autoimmune diseases including type-1 diabetes, rhematoid arthritis and multiple sclerosis. The therapeutic use of Treg cells, however, is so far hampered by the inefficiency of current protocols in making them accessible for genetic manipulations. We report here that TCR/CD3 stimulation that is accompanied by extensive CD28 costimulation makes human Treg cells susceptible to retroviral gene transfer ex vivo while preserving their properties in vitro and in vivo. To show the power of genetic manipulation of human Treg cells, we engineered ‘designer Treg cells’ by retroviral expression of a chimeric immunoreceptor with defined specificity, which activates Treg cells in a ligand-dependent manner to proliferate, to secrete high amounts of interleukin-10 and to repress an ongoing cytolytic T-cell response in vivo. The procedure in genetically modifying human Treg cells ex vivo will open a panel of applications for their use in the adoptive therapy of deregulated immune responses.

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Acknowledgements

We thank Birgit Hops, Frank Steiger and Petra Hofmann for technical assistance. This study was supported by the European Commission through the ATTACK project and the Fortune program of the Medical Faculty of the University of Cologne.

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Authors and Affiliations

  1. Zentrum für Molekulare Medizin Köln (ZMMK) and Klinik I für Innere Medizin, Labor Tumorgenetik, Universität zu Köln, Köln, Germany

    A A Hombach, D Kofler, G Rappl & H Abken

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  1. A A Hombach
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  2. D Kofler
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  3. G Rappl
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  4. H Abken
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Correspondence to A A Hombach.

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Hombach, A., Kofler, D., Rappl, G. et al. Redirecting human CD4+CD25+ regulatory T cells from the peripheral blood with pre-defined target specificity. Gene Ther 16, 1088–1096 (2009). https://doi.org/10.1038/gt.2009.75

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