Alloreactive regulatory T cells generated with retinoic acid prevent skin allograft rejection

Carolina Moore, Gabriela Tejon, Camila Fuentes, Yessia Hidalgo, Maria R. Bono, Paula Maldonado, Ricardo Fernandez, Kathryn J. Wood, Juan A. Fierro, Mario Rosemblatt, Daniela Sauma, Andrew Bushell

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)

Abstract

CD4+CD25+Foxp3+ regulatory T (Treg) cells mediate immunological self-tolerance and suppress immune responses. Retinoic acid (RA), a natural metabolite of vitamin A, has been reported to enhance the differentiation of Treg cells in the presence of TGF-β. In this study, we show that the co-culture of naive T cells from C57BL/6 mice with allogeneic antigen-presenting cells (APCs) from BALB/c mice in the presence of TGF-β, RA, and IL-2 resulted in a striking enrichment of Foxp3+ T cells. These RA in vitro-induced regulatory T (RA-iTreg) cells did not secrete Th1-, Th2-, or Th17-related cytokines, showed a nonbiased homing potential, and expressed several cell surface molecules related to Treg-cell suppressive potential. Accordingly, these RA-iTreg cells suppressed T-cell proliferation and inhibited cytokine production by T cells in in vitro assays. Moreover, following adoptive transfer, RA-iTreg cells maintained Foxp3 expression and their suppressive capacity. Finally, RA-iTreg cells showed alloantigen-specific immunosuppressive capacity in a skin allograft model in immunodeficient mice. Altogether, these data indicate that functional and stable allogeneic-specific Treg cells may be generated using TGF-β, RA, and IL-2. Thus, RA-iTreg cells may have a potential use in the development of more effective cellular therapies in clinical transplantation.

Original languageEnglish
Pages (from-to)452-463
Number of pages12
JournalEuropean Journal of Immunology
Volume45
Issue number2
DOIs
Publication statusPublished - 1 Feb 2015

Keywords

  • Allogeneic regulatory T cells
  • Homing
  • Retinoic acid
  • Tolerance
  • Transplantation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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