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

Resultado de la investigación: Contribución a una revistaArtículorevisión exhaustiva

24 Citas (Scopus)

Resumen

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.

Idioma originalInglés
Páginas (desde-hasta)452-463
Número de páginas12
PublicaciónEuropean Journal of Immunology
Volumen45
N.º2
DOI
EstadoPublicada - 1 feb 2015

Áreas temáticas de ASJC Scopus

  • Inmulogía y alergología
  • Inmunología

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