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Dendritic cell modification as a route to inhibiting corneal graft rejection by the indirect pathway of allorecognition
Dendritic cell (DC) modification is a potential strategy to induce clinical transplantation tolerance. We compared two DC modification strategies to inhibit allogeneic T-cell proliferation. In the first strategy, murine DCs were transduced with a lentiviral vector expressing CTLA4-KDEL, a fusion pro...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Blackwell Publishing Ltd
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3615172/ https://www.ncbi.nlm.nih.gov/pubmed/23212959 http://dx.doi.org/10.1002/eji.201242914 |
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author | Khan, Adnan Fu, Hongmei Tan, Lee Aun Harper, Jennifer E Beutelspacher, Sven C Larkin, Daniel F P Lombardi, Giovanna McClure, Myra O George, Andrew J T |
author_facet | Khan, Adnan Fu, Hongmei Tan, Lee Aun Harper, Jennifer E Beutelspacher, Sven C Larkin, Daniel F P Lombardi, Giovanna McClure, Myra O George, Andrew J T |
author_sort | Khan, Adnan |
collection | PubMed |
description | Dendritic cell (DC) modification is a potential strategy to induce clinical transplantation tolerance. We compared two DC modification strategies to inhibit allogeneic T-cell proliferation. In the first strategy, murine DCs were transduced with a lentiviral vector expressing CTLA4-KDEL, a fusion protein that prevents surface CD80/86 expression by retaining the co-stimulatory molecules within the ER. In the second approach, DCs were transduced to express the tryptophan-catabolising enzyme IDO. CTLA4-KDEL-expressing DCs induced anergy in alloreactive T cells and generated both CD4(+)CD25(+) and CD4(+)CD25(−) Treg cells (with direct and indirect donor allospecificity and capacity for linked suppression) both in vitro and in vivo. In contrast, T-cell unresponsiveness induced by IDO(+) DCs lacked donor specificity. In the absence of any immunosuppressive treatment, i.v. administration of CTLA4-KDEL-expressing DCs resulted in long-term survival of corneal allografts only when the DCs were capable of indirect presentation of alloantigen. This study demonstrates the therapeutic potential of CTLA4-KDEL-expressing DCs in tolerance induction. |
format | Online Article Text |
id | pubmed-3615172 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Blackwell Publishing Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-36151722013-04-04 Dendritic cell modification as a route to inhibiting corneal graft rejection by the indirect pathway of allorecognition Khan, Adnan Fu, Hongmei Tan, Lee Aun Harper, Jennifer E Beutelspacher, Sven C Larkin, Daniel F P Lombardi, Giovanna McClure, Myra O George, Andrew J T Eur J Immunol Immunomodulation Dendritic cell (DC) modification is a potential strategy to induce clinical transplantation tolerance. We compared two DC modification strategies to inhibit allogeneic T-cell proliferation. In the first strategy, murine DCs were transduced with a lentiviral vector expressing CTLA4-KDEL, a fusion protein that prevents surface CD80/86 expression by retaining the co-stimulatory molecules within the ER. In the second approach, DCs were transduced to express the tryptophan-catabolising enzyme IDO. CTLA4-KDEL-expressing DCs induced anergy in alloreactive T cells and generated both CD4(+)CD25(+) and CD4(+)CD25(−) Treg cells (with direct and indirect donor allospecificity and capacity for linked suppression) both in vitro and in vivo. In contrast, T-cell unresponsiveness induced by IDO(+) DCs lacked donor specificity. In the absence of any immunosuppressive treatment, i.v. administration of CTLA4-KDEL-expressing DCs resulted in long-term survival of corneal allografts only when the DCs were capable of indirect presentation of alloantigen. This study demonstrates the therapeutic potential of CTLA4-KDEL-expressing DCs in tolerance induction. Blackwell Publishing Ltd 2013-03 2012-12-04 /pmc/articles/PMC3615172/ /pubmed/23212959 http://dx.doi.org/10.1002/eji.201242914 Text en © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim http://creativecommons.org/licenses/by/2.5/ Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation. |
spellingShingle | Immunomodulation Khan, Adnan Fu, Hongmei Tan, Lee Aun Harper, Jennifer E Beutelspacher, Sven C Larkin, Daniel F P Lombardi, Giovanna McClure, Myra O George, Andrew J T Dendritic cell modification as a route to inhibiting corneal graft rejection by the indirect pathway of allorecognition |
title | Dendritic cell modification as a route to inhibiting corneal graft rejection by the indirect pathway of allorecognition |
title_full | Dendritic cell modification as a route to inhibiting corneal graft rejection by the indirect pathway of allorecognition |
title_fullStr | Dendritic cell modification as a route to inhibiting corneal graft rejection by the indirect pathway of allorecognition |
title_full_unstemmed | Dendritic cell modification as a route to inhibiting corneal graft rejection by the indirect pathway of allorecognition |
title_short | Dendritic cell modification as a route to inhibiting corneal graft rejection by the indirect pathway of allorecognition |
title_sort | dendritic cell modification as a route to inhibiting corneal graft rejection by the indirect pathway of allorecognition |
topic | Immunomodulation |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3615172/ https://www.ncbi.nlm.nih.gov/pubmed/23212959 http://dx.doi.org/10.1002/eji.201242914 |
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