Role of Allergic Conjunctivitis in Inducing Corneal Transplant Rejection




Reyes, Nancy Janet

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Corneal allografts are the most commonly transplanted solid organs in humans and have a success rate of over 90%. This low incidence of graft rejection is largely due to the unique properties of the eye that decrease the likelihood of mounting an immune response, a phenomenon called "immune privilege". Despite this characteristic, immune rejection remains the leading cause of corneal graft failure, indicating that immune privilege can be abolished. We used a model of corneal transplantation in which C57BL/6 corneal allografts transplanted to BALB/c mice experienced a 50% survival rate. This is in sharp contrast to the 100% rejection that occurs with other organ grafts exchanged between these two mouse strains. The 50% survival rate decreased to 0% in mice with ongoing allergic conjunctivitis. We set out to delineate the mechanisms by which allergic conjunctivitis abolishes immune privilege and results in corneal allograft rejection. Anterior chamber-associated immune deviation (ACAID) is initiated when foreign antigens, such as histocompatibility antigens sloughed from the cornea, enter the anterior chamber of the eye and induce a systemic down-regulation of immune responses. Studies have shown that abolishing ACAID increases the incidence of corneal allograft rejection. The hypothesis that allergic conjunctivitis abolished the induction of ACAID was tested and results showed that allergic conjunctivitis did not. Moreover, allergic conjunctivitis did not cause a qualitative or quantitative difference in cell-mediated immune responses to the donor’s alloantigens. Regulatory T cells (Tregs) have also been shown to be important in corneal allograft survival. Our results indicated that allergic conjunctivitis altered the Tregs that support corneal allograft survival. Th2 cytokines, namely IL-4, generated during allergic conjunctivitis, render effector cells resistant to the suppressive ability of Tregs. Furthermore, allergic conjunctivitis did not exacerbate corneal allograft rejection unless the host’s effector T cells were able to respond to IL-4. Moreover, corneal immune privilege was restored in short ragweed (SRW) pollen-sensitized, allergic mice if they were isolated from SRW pollen for 14 days after receiving a corneal allograft. These results suggest that the exacerbation of corneal allografts in allergic hosts is due to the production of IL-4, which renders effector T cells resistant to Treg suppression.

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