Purchase this article with an account.
Takaaki Hattori, Daniel R. Saban, Parisa Enami-Naeini, Toshinari Funaki, Hiroki Ueno, Amir R. Hajrasouliha, Sunil Chauhan, Reza Dana; Derivation And Use Of Tolerogenic Dendritic Cells Prolong Corneal Transplantation. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1140.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Utilization of tolerogenic dendritic cells (DCs) for suppression of immune responses, such as transplant rejection, is of significant interest. In this study, we determined the therapeutic effect of donor tolerogenic DCs (DCregs) on murine corneal allograft survival.
DCregs were generated from C57BL/6 bone marrow cells in the presence of GMCSF, IL-10 and TGF-β1. Expression of MHC-II and costimulatory molecules on DCregs were analyzed by flow cytometry. Donor DCregs were infused into BALB/c recipients 7 days before transplantation of C57BL/6 donor corneas. Three weeks post-transplantation, the number of effector T cells (IFN-γ+) or regulatory T cells (CD4+CD25+Foxp3+) in the draining lymph nodes were analyzed by flow cytometry. ELISPOT assay was performed at 3 weeks post-transplantation to measure the effect of DCreg infusion on direct and indirect pathways of allosensitization in transplanted recipients. Lastly, C57BL/6 mice corneas were orthotopically grafted into DCreg infused or untreated control BALB/c hosts and graft survival was measured for 8 weeks via slit-lamp biomicroscopy (n=6 mice per group).
DCregs expressed low levels of MHC-II and co-stimulatory molecules. DCreg infusion suppressed IFN-γ+ cells and increased CD4+CD25+Foxp3+ Tregs in draining lymph nodes. ELISPOT assay revealed that DCregs suppressed the indirect pathway of allosensitization, while there was also some effect on the direct pathway. Finally, infusion of donor DCregs prolonged corneal graft survival compared to untreated recipients (P<0.05).
Our data indicate that donor tolerogenic DCs prolong corneal allograft survival, primarily through suppression of the indirect pathway of allosensitization.
This PDF is available to Subscribers Only