The high‐risk corneal regraft model: a justification for tissue matching in humans. (11th February 2013)

• Record Type: Journal Article
• Authors: Vitova, Andrea; Kuffová, Lucia; Klaska, Izabela P.; Holan, Vladimir; Cornall, Richard J.; Forrester, John V.
• Is Part Of: Transplant international. Volume 26:Number 4(2013:Apr.)
• Page Start: 453
• Page End: 461
• Publication Date: 2013-02-11
• Subjects: Transplantation of organs, tissues, etc -- Periodicals; 617.95405
• DOI: 10.1111/tri.12055
• Languages: English
• ISSNs: 0934-0874

Abstract

<abstract abstract-type="main" id="tri12055-abs-0001"> <title>Summary</title> <p>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<sup>k</sup>) 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<sup>k</sup>), 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.</p> </abstract>