BDC12-4.1 T-cell receptor transgenic insulin-specific CD4 T cells are resistant to in vitro differentiation into functional Foxp3+ T regulatory cells

Ghanashyam Sarikonda, Georgia Fousteri, Sowbarnika Sachithanantham, Jacqueline F. Miller, Amy Dave, Therese Juntti, Ken T. Coppieters, Matthias Von Herrath

Research output: Contribution to journalArticlepeer-review

Abstract

The infusion of ex vivo-expanded autologous T regulatory (Treg) cells is potentially an effective immunotherapeutic strategy against graft-versus-host disease (GvHD) and several autoimmune diseases, such as type 1 diabetes (T1D). However, in vitro differentiation of antigen-specific T cells into functional and stable Treg (iTreg) cells has proved challenging. As insulin is the major autoantigen leading to T1D, we tested the capacity of insulin-specific T-cell receptor (TCR) transgenic CD4+ T cells of the BDC12-4.1 clone to convert into Foxp3+ iTreg cells. We found that in vitro polarization toward Foxp3+ iTreg was effective with a majority (>70%) of expanded cells expressing Foxp3. However, adoptive transfer of Foxp3+ BDC12-4.1 cells did not prevent diabetes onset in immunocompetent NOD mice. Thus, in vitro polarization of insulin-specific BDC12-4.1 TCR transgenic CD4+ T cells toward Foxp3+ cells did not provide dominant tolerance in recipient mice. These results highlight the disconnect between an in vitro acquired Foxp3+ cell phenotype and its associated in vivo regulatory potential.

Original languageEnglish
Article numbere112242
JournalPLoS One
Volume9
Issue number11
DOIs
Publication statusPublished - Nov 13 2014

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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