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Updated: Aug 14, 2025
Murine Corneal Transplantation: A Model to Study the Most Common Form of Solid Organ Transplantation
Published on: November 17, 2014
Conventional type I migratory CD103+ dendritic cells are required for corneal allograft survival
Tomas Blanco1, Rohan Bir Singh1, Hayate Nakagawa1
1Laboratory of Corneal Immunology, Transplantation, and Regeneration, Schepens Eye Research Institute of Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, USA.
Insights
Type 1 conventional dendritic cells (CD103+DC1) are crucial for corneal allograft survival. These cells suppress T helper 1 (Th1) immune responses, preventing rejection and promoting graft acceptance.
Area of Science:
- Immunology
- Transplantation Science
- Cellular Biology
Background:
- Corneal transplant rejection is mainly driven by T helper 1 (Th1) immune responses against the allograft.
- Type 1 conventional dendritic cells (CD103+DC1) are known to have immunosuppressive properties in tumor environments.
- The role of CD103+DC1 in allograft survival, particularly in corneal transplantation, remains largely unknown.
Purpose of the Study:
- To investigate the function of CD103+DC1 in suppressing Th1 alloreactivity in corneal allografts.
- To determine the impact of CD103+DC1 on allograft survival and host immune responses.
Main Methods:
- Assessed the infiltration and migration of host CD103+DC1 into corneal grafts and draining lymph nodes.
- Investigated the suppression of alloreactive CD4+ Th1 cells by CD103+DC1 via the programmed death-ligand 1 axis.
- Utilized systemic depletion of CD103+DC1 in allograft recipients and analyzed Th1 activation, Treg function, and allograft rejection rates.
- Examined peripheral Treg (pTreg) generation in CD103+DC1-depleted mice and assessed the efficacy of pTreg adoptive transfer.
Main Results:
- Host CD103+DC1 infiltrate corneal grafts and migrate to lymph nodes, suppressing alloreactive CD4+ Th1 cells through the PD-L1 axis.
- Systemic depletion of CD103+DC1 resulted in heightened Th1 responses, impaired Treg function, and accelerated allograft rejection.
- CD103+DC1-deficient mice failed to generate peripheral Tregs, and adoptive transfer of Tregs could not prevent rejection in these mice.
Conclusions:
- CD103+DC1 play a critical role in regulating host alloimmune responses following corneal transplantation.
- These dendritic cells are essential for inducing peripheral Tregs and maintaining allograft survival.
- Targeting CD103+DC1 may offer a novel therapeutic strategy to prevent corneal transplant rejection.
Abstract:
Corneal transplant rejection primarily occurs because of the T helper 1 (Th1) effector cell-mediated immune response of the host towards allogeneic tissue. The evidence suggests that type 1 migratory conventional CD103+ dendritic cells (CD103+DC1) acquire an immunosuppressive phenotype in the tumor environment; however, the involvement of CD103+DC1 in allograft survival continues to be an elusive question of great clinical significance in tissue transplantation. In this study, we assess the role of CD103+DC1 in suppressing Th1 alloreactivity against transplanted corneal allografts. The immunosuppressive function of CD103+DC1 has been extensively studied in non-transplantation settings. We found that host CD103+DC1 infiltrates the corneal graft and migrates to the draining lymph nodes to suppress alloreactive CD4+ Th1 cells via the programmed death-ligand 1 axis. The systemic depletion of CD103+ DC1 in allograft recipients leads to amplified Th1 activation, impaired Treg function, and increased rate of allograft rejection. Although allograft recipient Rag1 null mice reconstituted with naïve CD4+CD25- T cells efficiently generated peripheral Treg cells (pTreg), the CD103+DC1-depleted mice failed to generate pTreg. Furthermore, adoptive transfer of pTreg failed to rescue allografts in CD103+DC1-depleted recipients from rejection. These data demonstrate the critical role of CD103+DC1 in regulating host alloimmune responses.
