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Updated: Mar 24, 2026

Generation of Induced Regulatory T Cells from Primary Human Naïve and Memory T Cells
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Published on: April 16, 2012

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Distinctive Expression of Bcl-2 Factors in Regulatory T Cells Determines a Pharmacological Target to Induce

Sarah Sharon Gabriel1, Nina Bon1, Jin Chen1

  • 1Nephrology, Institute of Physiology, University of Zürich, Zürich, Switzerland; Division of Nephrology, University Hospital Zürich, Zürich, Switzerland.

Frontiers in Immunology
|March 15, 2016
PubMed

Distinctive molecular characteristics of functionally diverse lymphocyte populations may represent novel pharmacological targets for immunotherapy. The intrinsic apoptosis pathway is differently regulated among conventional and regulatory T cells (Tregs). Targeted pharmacological modulation of this pathway with a small molecule Bcl-2/Bcl-xL inhibitor (ABT-737) caused a selective depletion of effector T cells and a relative enrichment of Tregs in vivo. Treatment with ABT-737 resulted in a tolerogenic milieu, which was exploited to alleviate graft-versus-host disease, to prevent allograft rejection in a stringent fully MHC-mismatched skin transplantation model and to induce immunological tolerance in combination with bone marrow transplantation. This concept has the potential to find various applications for immunotherapy, since it allows pharmacologic exploitation of the immunomodulatory properties of Tregs without the need for cell manipulation ex vivo.

Keywords:
ABT-737Bcl-2Bcl-XLMcl-1apoptosisregulatory T cellstolerancetransplantation

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