Artículo de revista
Alloreactive regulatory T cells generated with retinoic acid prevent skin allograft rejection
Fecha
2015Registro en:
Eur. J. Immunol. 2015. 45: 452–463
DOI: 10.1002/eji.201444743
Autor
Moore, Carolina
Tejón, Gabriela
Fuentes, Camila
Hidalgo, Yessia
Bono Merino, María Rosa
Maldonado, Paula
Fernández, Ricardo
Wood, Kathryn
Fierro, Juan
Rosemblatt Silber, Mario César
Sauma Mahaluf, Daniela
Bushell, Andrew
Institución
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.