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Generation of Induced Regulatory T Cells from Primary Human Naïve and Memory T Cells
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Generation of Induced Regulatory T Cells from Primary Human Naïve and Memory T Cells

Published on: April 16, 2012

The role of 2 FOXP3 isoforms in the generation of human CD4+ Tregs

Sarah E Allan1, Laura Passerini, Rosa Bacchetta

  • 1Department of Surgery, University of British Columbia, and Immunity and Infection Research Centre, Vancouver Coastal Health Research Institute, Vancouver, British Columbia, Canada.

The Journal of Clinical Investigation
|October 8, 2005
PubMed

Insights

FOXP3 is crucial for regulatory T cell (Treg) development in mice. However, in humans, overexpressing FOXP3 alone or with its delta2 isoform did not effectively generate potent suppressor T cells in vitro.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cellular Biology

Background:

  • Regulatory T cells (Tregs), specifically CD4+ CD25+ Tregs, play a critical role in immune system regulation.
  • The transcription factor FOXP3 has been identified as essential for Treg development in mice.

Purpose of the Study:

  • To investigate whether FOXP3 can drive the generation of suppressive CD4+ CD25+ Tregs in humans.
  • To determine the role of FOXP3 and its human isoform FOXP3delta2 in inducing Treg suppressor function in vitro.

Main Methods:

  • Ectopic expression of FOXP3 and FOXP3delta2 in human CD4+ T cells.
  • Assessing Treg-associated cell surface markers and in vitro suppressor activity.
  • Measuring IL-2 production as an indicator of T cell activation.

Main Results:

  • Ectopic FOXP3 expression in human T cells induced hyporesponsiveness and suppressed IL-2 production but did not confer significant suppressor activity.
  • Ectopic expression of FOXP3delta2 also failed to induce suppressor T cell development.
  • Simultaneous overexpression of FOXP3 and FOXP3delta2 increased Treg markers but only modestly enhanced suppressor activity.

Conclusions:

  • Overexpression of FOXP3 alone or with FOXP3delta2 is insufficient to generate potent suppressor T cells in vitro in humans.
  • Additional factors beyond FOXP3 are likely required for the activation and differentiation of bona fide human Tregs.

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