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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-2 k ) 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-2 k ), 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. © 2013 The Authors Transplant International © 2013 European Society for Organ Transplantation. Published by Blackwell Publishing Ltd.

Original publication

DOI

10.1111/tri.12055

Type

Journal article

Journal

Transplant International

Publication Date

01/04/2013

Volume

26

Pages

453 - 461