Open AccessBDC12-4.1 T-Cell Receptor Transgenic Insulin-Specific CD4 T Cells Are Resistant to In Vitro Differentiation into Functional Foxp3+ T Regulatory Cells
Author(s) -
Ghanashyam Sarikonda,
Georgia Fousteri,
Sowbarnika Sachithanantham,
Jacqueline Miller,
Amy Dave,
Therese Juntti,
Ken Coppieters,
Matthias von Herrath
Publication year - 2014
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0112242
Subject(s) - foxp3 , adoptive cell transfer , t cell receptor , biology , microbiology and biotechnology , nod , immunology , interleukin 21 , il 2 receptor , t cell , immune system , in vivo , genetics
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.