September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
The Direct Pathway of T Cell Sensitization Mediate Corneal Graft Rejection in Absence of the Indirect Pathway in Low Risk Murine Allogeneic Corneal Transplantation
Author Affiliations & Notes
  • Maria Jose Lopez
    Ophthalmology, Tufts Medical Center, Boston, Massachusetts, United States
  • Victor Sendra
    Ophthalmology, Tufts Medical Center, Boston, Massachusetts, United States
  • Arsia Jamali
    Ophthalmology, Tufts Medical Center, Boston, Massachusetts, United States
  • Hamid-Reza Moein
    Ophthalmology, Tufts Medical Center, Boston, Massachusetts, United States
  • Deshea L Harris
    Ophthalmology, Tufts Medical Center, Boston, Massachusetts, United States
  • Pedram Hamrah
    Ophthalmology, Tufts Medical Center, Boston, Massachusetts, United States
  • Footnotes
    Commercial Relationships   Maria Lopez, None; Victor Sendra, None; Arsia Jamali, None; Hamid-Reza Moein, None; Deshea Harris, None; Pedram Hamrah, None
  • Footnotes
    Support  NIH K08-EY020575 (PH), NIH R01-EY022695 (PH), Research to Prevent Blindness Career Development Award (PH), Falk Medical Research Trust (PH).
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 1441. doi:
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      Maria Jose Lopez, Victor Sendra, Arsia Jamali, Hamid-Reza Moein, Deshea L Harris, Pedram Hamrah; The Direct Pathway of T Cell Sensitization Mediate Corneal Graft Rejection in Absence of the Indirect Pathway in Low Risk Murine Allogeneic Corneal Transplantation. Invest. Ophthalmol. Vis. Sci. 2016;57(12):1441.

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      © 2017 Association for Research in Vision and Ophthalmology.

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Abstract

Purpose : After corneal transplantation, alloreactive T cells are primed by donor or host dendritic cells (DCs) via the direct or indirect pathways to elicit T cell sensitization. In the murine model of ‘low risk’ corneal transplantation is well known that the indirect pathway of sensitization is dominant, resulting in rejection. The purpose of this study is to analyze the differential role of host and donor-derived DCs in corneal allotransplantation.

Methods : A murine allogeneic corneal transplantation model was used. Wild-type (WT) BALB/c mice corneas were used as donors and transplanted into WT C57BL/6 (B6) or CD11c+-DTR-GFP recipients. The CD11c+-DTR-GFP mice received subconjunctival (SC) injection of diphtheria toxin (DT) every 48 hours to locally deplete DCs, starting one day prior to transplantation. At day 14 after corneal transplantation, clinical scoring of the graft was performed and ipsilateral draining lymph nodes (dLNs) were harvested, single cell suspensions obtained and analyzed by flow cytometry for CD3, CD4, CD25, and Foxp3.

Results : At day 14 after corneal transplantation, allografts in which the recipients were depleted for host DCs demonstrated 100% rejection. Lymphocytes isolated from dLNs in this group showed lower frequencies of CD4+CD25+Foxp3+ T regulatory cells (Tregs) compared to allogeneic controls (p=0.03). No significant difference was observed in the mean fluorescence intensity (MFI) of Foxp3 in Tregs of these groups.

Conclusions : After local depletion of host-derived DCs, in which the indirect pathway of T cell priming is abolished, graft rejection is mediated by donor-derived DCs. Donor-derived DCs alone lead to decreased Foxp3 frequencies and suppressor function of Tregs after corneal transplantation. In ‘low risk’ corneal transplantation the direct pathway results in corneal graft rejection in the absence of the indirect pathway.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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