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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-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.
  • 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. (en)
Title
  • The high-risk corneal regraft model: a justification for tissue matching in humans
  • The high-risk corneal regraft model: a justification for tissue matching in humans (en)
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  • The high-risk corneal regraft model: a justification for tissue matching in humans
  • The high-risk corneal regraft model: a justification for tissue matching in humans (en)
skos:notation
  • RIV/68378050:_____/13:00392147!RIV14-AV0-68378050
http://linked.open...avai/riv/aktivita
http://linked.open...avai/riv/aktivity
  • I
http://linked.open...iv/cisloPeriodika
  • 4
http://linked.open...vai/riv/dodaniDat
http://linked.open...aciTvurceVysledku
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http://linked.open...titaPredkladatele
http://linked.open...dnocenehoVysledku
  • 77435
http://linked.open...ai/riv/idVysledku
  • RIV/68378050:_____/13:00392147
http://linked.open...riv/jazykVysledku
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  • accelerated rejection; corneal transplantation; dendritic cells; regraft; T-cell memory; transgenic mouse (en)
http://linked.open.../riv/klicoveSlovo
http://linked.open...odStatuVydavatele
  • GB - Spojené království Velké Británie a Severního Irska
http://linked.open...ontrolniKodProRIV
  • [B42250DC52D4]
http://linked.open...i/riv/nazevZdroje
  • Transplant International
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http://linked.open...UplatneniVysledku
http://linked.open...v/svazekPeriodika
  • 26
http://linked.open...iv/tvurceVysledku
  • Holáň, Vladimír
  • Cornall, R. J.
  • Forrester, J. V.
  • Klaska, I.
  • Kuffova, L.
  • Vitova, A.
http://linked.open...ain/vavai/riv/wos
  • 000316633100018
issn
  • 0934-0874
number of pages
http://bibframe.org/vocab/doi
  • 10.1111/tri.12055
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