The high-risk corneal regraft model: a justification for tissue matching in humans

Andrea Vitova, Lucia Kuffova, Izabela P. Klaska, Vladimir Holan, Richard J. Cornall, John V. Forrester

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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-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.
Original languageEnglish
Pages (from-to)453-461
Number of pages9
JournalTransplant International
Volume26
Issue number4
Early online date11 Feb 2013
DOIs
Publication statusPublished - Apr 2013

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Keywords

  • accelerated rejection
  • corneal transplantation
  • dendritic cells
  • regraft
  • T-cell memory
  • transgenic mouse

Cite this

Vitova, A., Kuffova, L., Klaska, I. P., Holan, V., Cornall, R. J., & Forrester, J. V. (2013). The high-risk corneal regraft model: a justification for tissue matching in humans. Transplant International, 26(4), 453-461. https://doi.org/10.1111/tri.12055