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

0392147 - ÚMG 2014 RIV GB eng J - Journal Article
Vitova, A. - Kuffova, L. - Klaska, I. - Holáň, Vladimír - Cornall, R.J. - Forrester, J.V.
The high-risk corneal regraft model: a justification for tissue matching in humans.
Transplant International. Roč. 26, č. 4 (2013), s. 453-461. ISSN 0934-0874. E-ISSN 1432-2277
Institutional support: RVO:68378050
Keywords : accelerated rejection * corneal transplantation * dendritic cells * regraft * T-cell memory * transgenic mouse
Subject RIV: EB - Genetics ; Molecular Biology
Impact factor: 3.120, year: 2013

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 5060days. Graft rejection incidence was maximized (100%) and tempo accelerated (27days) 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 (38days) 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 naive 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.
Permanent Link: http://hdl.handle.net/11104/0228418