Abstract
Abstract: :
Purpose: Allergic conjunctivitis is associated with an increased risk of corneal graft rejection in human keratoplasty patients. This study examined the effect of allergic conjunctivitis on the incidence, tempo, and mechanisms of corneal allograft rejection. Methods: Allergic conjunctivitis was induced in BALB/c mice by immunization and repeated topical challenge with short ragweed (SRW) pollen. Full–thickness penetrating keratoplasty was performed on atopic hosts using full MHC or minors–only mismatched donors. Th1 and Th2 cytokine production in lymphoid tissue was measured by ELISA. Allospecific delayed–type hypersensitivity (DTH) responses were determined by an ear–swelling assay. Histology and immunohistochemistry (IHC) were performed to characterize the cellular infiltrate of rejected corneal grafts. Results: Fully histoincompatible C57BL/6 allografts placed on SRW pollen–challenged eyes were rejected in 100% of recipients with a median survival time (MST) of 30 days (vs. 50% rejection and MST of 54 days in normal hosts). Minors–only mismatched B10.D2 allografts placed on atopic hosts were also rejected in 100% of the recipients with an MST of 21 days (vs. 62% rejection and MST of 37 days in normal hosts). Syngeneic grafts in atopic hosts did not reject. Rejected grafts in atopic hosts were infiltrated with eosinophils and mononuclear cells. Atopic hosts produced DTH responses to donor alloantigens in vivo and produced IL–4, IL–5, and IFN–gamma in response to donor alloantigens in vitro. IHC revealed both Th1 and Th2 cells in the rejected grafts of atopic hosts, whereas normal hosts had mainly a Th1 infiltrate. When C57BL/6 allografts were placed into the contralateral eye (not challenged with ragweed) of atopic hosts, the rejection profile was identical to that seen in the challenged eye. A similar pattern of T cell infiltrate was seen in these eyes; however, no eosinophils were present. Conclusions: Preexisting atopy increases the risk for immune rejection of corneal allografts, regardless of MHC matching. Increased rejection involves Th1 and Th2 cell populations. Eosinophils are present, but may not play a significant role in rejection.
Keywords: transplantation • inflammation • immune tolerance/privilege