April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
Derivation And Use Of Tolerogenic Dendritic Cells Prolong Corneal Transplantation
Author Affiliations & Notes
  • Takaaki Hattori
    Ophthalmology, Tokyo Medical University, Tokyo, Japan
    Schepens Eye Research Institute, Harvard Medical School, Boston, Massachusetts
  • Daniel R. Saban
    Schepens Eye Research Institute, Harvard Medical School, Boston, Massachusetts
  • Parisa Enami-Naeini
    Schepens Eye Research Institute, Harvard Medical School, Boston, Massachusetts
  • Toshinari Funaki
    Schepens Eye Research Institute, Harvard Medical School, Boston, Massachusetts
    Ophthalmology, Juntendo Univ School of Medicine, Bunkyo-ku, Japan
  • Hiroki Ueno
    Schepens Eye Research Institute, Harvard Medical School, Boston, Massachusetts
    Ophthalmology, Schepens Eye Research Institute, Boston, Massachusetts
  • Amir R. Hajrasouliha
    Schepens Eye Research Institute, Harvard Medical School, Boston, Massachusetts
  • Sunil Chauhan
    Schepens Eye Research Institute, Harvard Medical School, Boston, Massachusetts
  • Reza Dana
    MEEI/SERI Harvard Ophthalmology, Boston, Massachusetts
  • Footnotes
    Commercial Relationships  Takaaki Hattori, None; Daniel R. Saban, None; Parisa Enami-Naeini, None; Toshinari Funaki, None; Hiroki Ueno, None; Amir R. Hajrasouliha, None; Sunil Chauhan, None; Reza Dana, None
  • Footnotes
    Support  NEI R01- EY20889, Eye Bank Association of America
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 1140. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      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)

      ×
  • Supplements
Abstract

Purpose: : 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.

Methods: : 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).

Results: : 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).

Conclusions: : Our data indicate that donor tolerogenic DCs prolong corneal allograft survival, primarily through suppression of the indirect pathway of allosensitization.

Keywords: transplantation • immune tolerance/privilege • cornea: basic science 
×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×