title: The high-risk corneal regraft model: a justification for tissue matching in humans.
abstract: Models of high-risk corneal graft rejection involve neovascularization induced via innate immune responses, e.g., suture-mediated trauma. We describe a model of high-risk corneal graft rejection using corneal graft donor-recipient pairing based on a single-antigen disparity. Donor corneas from transgenic mice on B10.BR (H-2k ) background, in which hen-egg lysozyme (HEL) as a membrane-bound antigen (mHEL) was expressed under the major histocompatibility complex (MHC) class I promoter (KLK-mHEL, H-2k), were transplanted into wild type B10.BR recipient mice. Unmanipulated wild type recipient mice rejected KLK-mHEL grafts (39%) slowly over 50-60 days. Graft rejection incidence was maximized (100%) and tempo accelerated (27 days) by priming with HEL-pulsed syngeneic dendritic cells and less so by increasing T-cell precursor frequency. Rejection also reached maximum levels (100%) and tempo (3-8 days) when mice which had rejected a first graft ('rejectors') were regrafted, and was associated with induction of HEL-specific memory T cells. In contrast, 'acceptors' rejected a second graft at rates and tempo similar to naïve mice. These data reveal the importance of (i) donor MHC antigens as alloantigens for indirect recognition, (ii) alloantigen-specific memory in high-risk graft rejection involving regrafts, and (iii) suggest a role for tissue matching in human corneal graft to avoid sensitization to donor MHC antigens.
authors: Section of Immunology and Infection, Division of Applied Medicine, University of Aberdeen, Aberdeen, UK.
authors: Andrea
authors: A
authors: Vitova
authors: Lucia
authors: L
authors: Kuffová
authors: Izabela P
authors: IP
authors: Klaska
authors: Vladimir
authors: V
authors: Holan
authors: Richard J
authors: RJ
authors: Cornall
authors: John V
authors: JV
authors: Forrester
mesh_terms: D000818:Animals; D016039:Corneal Transplantation / Q000009:adverse effects; D006084:Graft Rejection; D006650:Histocompatibility Testing; D006801:Humans; D007156:Immunologic Memory; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D023421:Models, Animal; D009113:Muramidase / Q000276:immunology; D012306:Risk; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D009113:Muramidase