Lloyd J A D'Orsogna

Publications (3)15.36 Total impact

• Article: Screening of viral specific T-cell lines for HLA alloreactivity prior to adoptive immunotherapy may prevent GvHD.

  Lloyd J A D'Orsogna, Dave L Roelen, Ilias I N Doxiadis, Frans H J Claas
  Transplant Immunology 04/2011; 24(3):141. · 1.46 Impact Factor
• Source

  Available from: Cees van Kooten

  Article: Tissue specificity of cross-reactive allogeneic responses by EBV EBNA3A-specific memory T cells.

  Lloyd J A D'Orsogna, Dave L Roelen, Ellen M W van der Meer-Prins, Pieter van der Pol, Marry E Franke-van Dijk, Michael Eikmans, Jacqy Anholts, Jamie Rossjohn, James McCluskey, Arend Mulder, Cees van Kooten, Ilias I N Doxiadis, Frans H J Claas
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  ABSTRACT: The crossreactivity of Epstein-Barr virus (EBV Epstein-Barr virus nuclear antigen 3A [EBNA3A])-specific CD8 T cells against allogeneic human leukocyte antigen (HLA)-B*44:02 has been shown to be dependent on presentation of self-peptide EEYLQAFTY by the target antigen. In this study, we report that allogeneic HLA-B*44:02 proximal tubular epithelial cells (PTECs) and human umbilical vein endothelial cells (HUVECs) are poor targets for EBV EBNA3A-specific T cells. The EEY peptide was exogenously loaded onto HLA-B*44:02 and HLA-B*44:03-expressing PTECs and HUVECs. EEY-peptide-loaded, and unloaded, PTECs and HUVECs were then incubated with serial dilutions of our EBNA3A T-cell clone, in a cytotoxicity assay. Although HLA-B*44:02-expressing PTECs were specifically lysed in proportion to the effector/target ratio by the EBNA3A T-cell clone, without peptide loading, lysis was greatly increased by exogenous EEY peptide loading (15% vs. 75%; P<0.0001). HLA-B*44:02-expressing HUVECs were only lysed when loaded with exogenous EEY peptide (0% vs. 64%; P<0.0001). Lack of HLA expression and lack of ABCD3 gene expression were excluded as a cause for these results. PTECs and HUVECs were specifically targeted by another alloreactive T-cell clone without exogenous peptide loading, suggesting that the lack of recognition of HLA-B*44:02 epithelial and endothelial cells by the EBV EBNA3A T-cell clone was due to lack of EEYLQAFTY peptide presentation. Tissue-specific (peptide dependent) alloreactivity may have important implications for transplantation monitoring and rejection.
  Transplantation 03/2011; 91(5):494-500. · 4.00 Impact Factor
• Article: Allo-HLA reactivity of virus-specific memory T cells is common.

  Avital L Amir, Lloyd J A D'Orsogna, Dave L Roelen, Marleen M van Loenen, Renate S Hagedoorn, Renate de Boer, Menno A W G van der Hoorn, Michel G D Kester, Ilias I N Doxiadis, J H Frederik Falkenburg, Frans H J Claas, Mirjam H M Heemskerk
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  ABSTRACT: Graft-versus-host disease and graft rejection are major complications of allogeneic HLA-mismatched stem cell transplantation or organ transplantation that are caused by alloreactive T cells. Because a range of acute viral infections have been linked to initiating these complications, we hypothesized that the cross-reactive potential of virus-specific memory T cells to allogeneic (allo) HLA molecules may be able to mediate these complications. To analyze the allo-HLA reactivity, T cells specific for Epstein-Barr virus, cytomegalovirus, varicella zoster virus, and influenza virus were tested against a panel of HLA-typed target cells, and target cells transduced with single HLA molecules. Eighty percent of T-cell lines and 45% of virus-specific T-cell clones were shown to cross-react against allo-HLA molecules. The cross-reactivity of the CD8 and CD4 T-cell clones was directed primarily against HLA class I and II, respectively. However, a restricted number of CD8 T cells exhibited cross-reactivity to HLA class II. T-cell receptor (TCR) gene transfer confirmed that allo-HLA reactivity and virus specificity were mediated via the same TCR. These results demonstrate that a substantial proportion of virus-specific T cells exert allo-HLA reactivity, which may have important clinical implications in transplantation settings as well as adoptive transfer of third-party virus-specific T cells.
  Blood 02/2010; 115(15):3146-57. · 9.90 Impact Factor