July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Local Delivery of Regulatory T Cells Promotes Corneal Allograft Survival
Author Affiliations & Notes
  • Chunyi Shao
    Schepens Eye Research Institute, Massachusetts Eye & Ear Infirmary, Harvard Medical School, Boston, Massachusetts, United States
    Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University Shool of Medicine, Shanghai, China
  • Yihe Chen
    Schepens Eye Research Institute, Massachusetts Eye & Ear Infirmary, Harvard Medical School, Boston, Massachusetts, United States
  • Takeshi Nakao
    Schepens Eye Research Institute, Massachusetts Eye & Ear Infirmary, Harvard Medical School, Boston, Massachusetts, United States
  • Afsaneh Amouzegar
    Schepens Eye Research Institute, Massachusetts Eye & Ear Infirmary, Harvard Medical School, Boston, Massachusetts, United States
  • Jia Yin
    Schepens Eye Research Institute, Massachusetts Eye & Ear Infirmary, Harvard Medical School, Boston, Massachusetts, United States
  • Maryam Tahvildari
    Schepens Eye Research Institute, Massachusetts Eye & Ear Infirmary, Harvard Medical School, Boston, Massachusetts, United States
  • Sunil Chauhan
    Schepens Eye Research Institute, Massachusetts Eye & Ear Infirmary, Harvard Medical School, Boston, Massachusetts, United States
  • Reza Dana
    Schepens Eye Research Institute, Massachusetts Eye & Ear Infirmary, Harvard Medical School, Boston, Massachusetts, United States
  • Footnotes
    Commercial Relationships   Chunyi Shao, None; Yihe Chen, None; Takeshi Nakao, None; Afsaneh Amouzegar, None; Jia Yin, None; Maryam Tahvildari, None; Sunil Chauhan, None; Reza Dana, None
  • Footnotes
    Support  This study was supported by the National Institutes of Health/National Eye Institute Grant R01 EY012963 to Dr. Reza Dana.
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 2574. doi:
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      Chunyi Shao, Yihe Chen, Takeshi Nakao, Afsaneh Amouzegar, Jia Yin, Maryam Tahvildari, Sunil Chauhan, Reza Dana; Local Delivery of Regulatory T Cells Promotes Corneal Allograft Survival. Invest. Ophthalmol. Vis. Sci. 2018;59(9):2574.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Regulatory T cell (Tregs)-based immunotherapies have been used as a novel strategy to promote graft survival in several organs. However, the therapeutic efficacy of local delivery of Tregs has not been thoroughly studied in corneal transplantation. We herein investigated the kinetics of migration of subconjunctivally-injected Tregs and their role in promoting corneal allograft survival.

Methods : To determine the kinetics of distribution of injected Tregs, GFP+CD4+CD25+ Tregs were isolated from draining lymph nodes (DLNs) of GFP transgenic mice, and were subconjunctivally injected to graft recipients immediately after allogeneic corneal transplantation. Next, either CD4+CD25+ Tregs or conventional T cells (Tconv, as the control) was locally injected to graft recipients. The frequencies of MHC-II+CD11b+ antigen presenting cells (APCs) in the corneas and DLNs, IFNγ+CD4+ Th1 cells in the DLNs, and CD45+ cells in the graft were evaluated on day 14 after transplantation using flow cytometry. Additionally, the mRNA and protein expression of IFNγ, IL-10 and TGF-ß in the grafts were assessed using RT-PCR and ELISA, respectively. Finally, corneal allograft survival was determined by weekly evaluation of graft opacity scores for 10 weeks.

Results : Subconjunctivally injected Tregs were detected in the ipsilateral cornea and DLNs of graft recipients as early as 6 hours post-injection. Treatment with Tregs significantly decreased the frequencies of mature APCs in the cornea (p=0.032) and DLNs (p=0.002), suppressed Th1 cell frequencies in the DLNs (p=0.017), and inhibited CD45+ cell infiltration to the grafts (p=0.016) compared to Tconv-treated controls. Additionally, Treg-treated recipients demonstrated significantly reduced expression of pro-inflammatory cytokine IFNγ (p=0.029), and enhanced expression of immunosuppressive cytokines IL-10 and TGF-ß in the cornea compared to the control group (p=0.029 and p=0.057, respectively). Finally, Treg-treated recipients demonstrated significantly higher graft survival rates compared to Tconv-treated controls (p=0.03).

Conclusions : Our data demonstrate that subconjunctivally delivered Tregs migrate to the cornea and draining lymph nodes of graft recipients where they suppress antigen presenting cell maturation and T cell allosensitization, and promote allograft survival. Our study suggests that local delivery of Tregs could be a promising strategy in preventing corneal allograft rejection.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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