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PLoS One. 2014 Nov 13;9(11):e112242. doi: 10.1371/journal.pone.0112242. eCollection 2014.

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

Author information

1
Diabetes Center, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA.
2
Type 1 Diabetes R&D center, Novo Nordisk Inc., Seattle, Washington, USA.
3
Diabetes Center, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA; Type 1 Diabetes R&D center, Novo Nordisk Inc., Seattle, Washington, USA.

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.

PMID:
25393309
PMCID:
PMC4231041
DOI:
10.1371/journal.pone.0112242
[Indexed for MEDLINE]
Free PMC Article

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