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Ex Vivo Generation of Human Alloantigen-Specific Regulatory T Cells from CD4(pos)CD25(high) T Cells for Immunotherapy

BACKGROUND: Regulatory T cell (Treg) based immunotherapy is a potential treatment for several immune disorders. By now, this approach proved successful in preclinical animal transplantation and auto-immunity models. In these models the success of Treg based immunotherapy crucially depends on the ant...

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Detalles Bibliográficos
Autores principales: Peters, Jorieke H., Hilbrands, Luuk B., Koenen, Hans J. P. M., Joosten, Irma
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2376059/
https://www.ncbi.nlm.nih.gov/pubmed/18493605
http://dx.doi.org/10.1371/journal.pone.0002233
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author Peters, Jorieke H.
Hilbrands, Luuk B.
Koenen, Hans J. P. M.
Joosten, Irma
author_facet Peters, Jorieke H.
Hilbrands, Luuk B.
Koenen, Hans J. P. M.
Joosten, Irma
author_sort Peters, Jorieke H.
collection PubMed
description BACKGROUND: Regulatory T cell (Treg) based immunotherapy is a potential treatment for several immune disorders. By now, this approach proved successful in preclinical animal transplantation and auto-immunity models. In these models the success of Treg based immunotherapy crucially depends on the antigen-specificity of the infused Treg population. For the human setting, information is lacking on how to generate Treg with direct antigen-specificity ex vivo to be used for immunotherapy. METHODOLOGY/PRINCIPAL FINDINGS: Here, we demonstrate that in as little as two stimulation cycles with HLA mismatched allogeneic stimulator cells and T cell growth factors a very high degree of alloantigen-specificity was reached in magnetic bead isolated human CD4(pos)CD25(high) Treg. Efficient increases in cell numbers were obtained. Primary allogeneic stimulation appeared a prerequisite in the generation of alloantigen-specific Treg, while secondary allogeneic or polyclonal stimulation with anti-CD3 plus anti-CD28 monoclonal antibodies enriched alloantigen-specificity and cell yield to a similar extent. CONCLUSIONS/SIGNIFICANCE: The ex vivo expansion protocol that we describe will very likely increase the success of clinical Treg-based immunotherapy, and will help to induce tolerance to selected antigens, while minimizing general immune suppression. This approach is of particular interest for recipients of HLA mismatched transplants.
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spelling pubmed-23760592008-05-21 Ex Vivo Generation of Human Alloantigen-Specific Regulatory T Cells from CD4(pos)CD25(high) T Cells for Immunotherapy Peters, Jorieke H. Hilbrands, Luuk B. Koenen, Hans J. P. M. Joosten, Irma PLoS One Research Article BACKGROUND: Regulatory T cell (Treg) based immunotherapy is a potential treatment for several immune disorders. By now, this approach proved successful in preclinical animal transplantation and auto-immunity models. In these models the success of Treg based immunotherapy crucially depends on the antigen-specificity of the infused Treg population. For the human setting, information is lacking on how to generate Treg with direct antigen-specificity ex vivo to be used for immunotherapy. METHODOLOGY/PRINCIPAL FINDINGS: Here, we demonstrate that in as little as two stimulation cycles with HLA mismatched allogeneic stimulator cells and T cell growth factors a very high degree of alloantigen-specificity was reached in magnetic bead isolated human CD4(pos)CD25(high) Treg. Efficient increases in cell numbers were obtained. Primary allogeneic stimulation appeared a prerequisite in the generation of alloantigen-specific Treg, while secondary allogeneic or polyclonal stimulation with anti-CD3 plus anti-CD28 monoclonal antibodies enriched alloantigen-specificity and cell yield to a similar extent. CONCLUSIONS/SIGNIFICANCE: The ex vivo expansion protocol that we describe will very likely increase the success of clinical Treg-based immunotherapy, and will help to induce tolerance to selected antigens, while minimizing general immune suppression. This approach is of particular interest for recipients of HLA mismatched transplants. Public Library of Science 2008-05-21 /pmc/articles/PMC2376059/ /pubmed/18493605 http://dx.doi.org/10.1371/journal.pone.0002233 Text en Peters et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Peters, Jorieke H.
Hilbrands, Luuk B.
Koenen, Hans J. P. M.
Joosten, Irma
Ex Vivo Generation of Human Alloantigen-Specific Regulatory T Cells from CD4(pos)CD25(high) T Cells for Immunotherapy
title Ex Vivo Generation of Human Alloantigen-Specific Regulatory T Cells from CD4(pos)CD25(high) T Cells for Immunotherapy
title_full Ex Vivo Generation of Human Alloantigen-Specific Regulatory T Cells from CD4(pos)CD25(high) T Cells for Immunotherapy
title_fullStr Ex Vivo Generation of Human Alloantigen-Specific Regulatory T Cells from CD4(pos)CD25(high) T Cells for Immunotherapy
title_full_unstemmed Ex Vivo Generation of Human Alloantigen-Specific Regulatory T Cells from CD4(pos)CD25(high) T Cells for Immunotherapy
title_short Ex Vivo Generation of Human Alloantigen-Specific Regulatory T Cells from CD4(pos)CD25(high) T Cells for Immunotherapy
title_sort ex vivo generation of human alloantigen-specific regulatory t cells from cd4(pos)cd25(high) t cells for immunotherapy
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2376059/
https://www.ncbi.nlm.nih.gov/pubmed/18493605
http://dx.doi.org/10.1371/journal.pone.0002233
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