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Evidence of indirect allorecognition of HLA /non-HLA antigens expressed by bronchial epithelial cells from lung transplant recipients

Vincent Bunel, Severine Letuve, Marina Pretolani, Chantal Schenowitz, Edgardo Carosella, Nathalie Rouass-Freiss, Olivier Brugiere
European Respiratory Journal 2016 48: PA4635; DOI: 10.1183/13993003.congress-2016.PA4635
Vincent Bunel
1IMETI, SRHI, Hôpital Saint-Louis, CEA, Paris, France
2Université Paris Diderot, Sorbonne Paris Cité, Paris, France
3UMR 1152, LabEx Inflamex, DHU Fire, INSERM, Paris, France
4Service de Pneumologie B et de Transplantation Pulmonaire, Hôpital Bichat-Claude Bernard, APHP, Paris, France
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Severine Letuve
2Université Paris Diderot, Sorbonne Paris Cité, Paris, France
3UMR 1152, LabEx Inflamex, DHU Fire, INSERM, Paris, France
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Marina Pretolani
2Université Paris Diderot, Sorbonne Paris Cité, Paris, France
3UMR 1152, LabEx Inflamex, DHU Fire, INSERM, Paris, France
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Chantal Schenowitz
1IMETI, SRHI, Hôpital Saint-Louis, CEA, Paris, France
2Université Paris Diderot, Sorbonne Paris Cité, Paris, France
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Edgardo Carosella
1IMETI, SRHI, Hôpital Saint-Louis, CEA, Paris, France
2Université Paris Diderot, Sorbonne Paris Cité, Paris, France
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Nathalie Rouass-Freiss
1IMETI, SRHI, Hôpital Saint-Louis, CEA, Paris, France
2Université Paris Diderot, Sorbonne Paris Cité, Paris, France
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Olivier Brugiere
1IMETI, SRHI, Hôpital Saint-Louis, CEA, Paris, France
2Université Paris Diderot, Sorbonne Paris Cité, Paris, France
3UMR 1152, LabEx Inflamex, DHU Fire, INSERM, Paris, France
4Service de Pneumologie B et de Transplantation Pulmonaire, Hôpital Bichat-Claude Bernard, APHP, Paris, France
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Abstract

Survival after lung transplantation (LTx) remains limited by the occurrence of bronchiolitis obliterans (BO), thought to be a form of chronic rejection. In BO, an indirect allorecognition of both HLA and non-HLA antigens (Ags) expressed by bronchial epithelial cells (BEC) is highly suspected as a crucial trigger for BECs damages, although levels of proof remain weak.

We here investigated the indirect allorecognition of Ags expressed by BEC in an original ex-vivo model established from samples of LTx recipients (LTxR). To reproduce the immune crosstalk that may occur in patients, 3 distinct cell types originated from the same LTxR were used: allogenic BECs (graft cells) in primary cultures, monocyte derived dendritic cells (DCs) and peripheral T cells. Mixed lymphocyte reactions were performed between T cells (responding cells) and DCs (stimulating cells) that had been or not previously loaded with Ags such as alloBECs lysates (n=10) or tetanus toxoid (TT) (n=6) as Ag positive control. Four healthy individuals were used as controls with TT-loaded DCs.

In LTxR, T-cell proliferation was increased by 49% [16-87%] when DCs loaded with alloBEC lysates were used. TT-loaded DCs increased T-cell proliferation by 51% [9-97]% in controls, but only by 4% [0-76%] in LTxR. These measures were highly variable in both patients and controls.

This ex-vivo model allowed us to demonstrate that LTxR display a specific T-cell response against alloBECs Ags through indirect allorecognition mechanism. Further objectives are the ability of this model to early predict BO in LTxR and to gain insight into the respective role of HLA and non-HLA Ags from BECs in alloreactivity.

  • Immunology
  • Transplantation
  • Dentritic cell
  • Copyright ©the authors 2016
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Evidence of indirect allorecognition of HLA /non-HLA antigens expressed by bronchial epithelial cells from lung transplant recipients
Vincent Bunel, Severine Letuve, Marina Pretolani, Chantal Schenowitz, Edgardo Carosella, Nathalie Rouass-Freiss, Olivier Brugiere
European Respiratory Journal Sep 2016, 48 (suppl 60) PA4635; DOI: 10.1183/13993003.congress-2016.PA4635

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Evidence of indirect allorecognition of HLA /non-HLA antigens expressed by bronchial epithelial cells from lung transplant recipients
Vincent Bunel, Severine Letuve, Marina Pretolani, Chantal Schenowitz, Edgardo Carosella, Nathalie Rouass-Freiss, Olivier Brugiere
European Respiratory Journal Sep 2016, 48 (suppl 60) PA4635; DOI: 10.1183/13993003.congress-2016.PA4635
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More in this TOC Section

  • Differences in the lipidomic profile of bronchial washing (BW) and bronchoalveolar lavage (BAL) in lung transplanted patients
  • Diffusion capacity as a predictor of prognosis after onset of CLAD
  • Orthotopic lung transplantation in a single-mismatch-based mouse model shows signs of chronic lung allograft dyfunction (CLAD)
Show more 8.2 Transplantation

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