T cells fail to develop in the human skin-cell explants system; an inconvenient truth
<p>Abstract</p> <p>Background</p> <p>Haplo-identical hematopoietic stem cell (HSC) transplantation is very successful in eradicating haematological tumours, but the long post-transplant T-lymphopenic phase is responsible for high morbidity and mortality rates. Clark <...
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Format: | Article |
Language: | English |
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BMC
2011-02-01
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Series: | BMC Immunology |
Online Access: | http://www.biomedcentral.com/1471-2172/12/17 |
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author | Vanderlocht Joris Lumeij Stijn BJ Tonnaer Siebe van der Stegen Sjoukje JC Huijskens Mirelle JAJ Van Elssen Catharina HMJ Meek Bob Kirkland Mark A Hesselink Reinout Germeraad Wilfred TV Bos Gerard MJ |
author_facet | Vanderlocht Joris Lumeij Stijn BJ Tonnaer Siebe van der Stegen Sjoukje JC Huijskens Mirelle JAJ Van Elssen Catharina HMJ Meek Bob Kirkland Mark A Hesselink Reinout Germeraad Wilfred TV Bos Gerard MJ |
author_sort | Vanderlocht Joris |
collection | DOAJ |
description | <p>Abstract</p> <p>Background</p> <p>Haplo-identical hematopoietic stem cell (HSC) transplantation is very successful in eradicating haematological tumours, but the long post-transplant T-lymphopenic phase is responsible for high morbidity and mortality rates. Clark <it>et al. </it>have described a skin-explant system capable of producing host-tolerant donor-HSC derived T-cells. Because this T-cell production platform has the potential to replenish the T-cell levels following transplantation, we set out to validate the skin-explant system.</p> <p>Results</p> <p>Following the published procedures, while using the same commercial components, it was impossible to reproduce the skin-explant conditions required for HSC differentiation towards mature T-cells. The keratinocyte maturation procedure resulted in fragile cells with minimum expression of delta-like ligand (DLL). In most experiments the generated cells failed to adhere to carriers or were quickly outcompeted by fibroblasts. Consequently it was not possible to reproduce cell-culture conditions required for HSC differentiation into functional T-cells. Using cell-lines over-expressing DLL, we showed that the antibodies used by Clark <it>et al. </it>were unable to detect native DLL, but instead stained 7AAD<sup>+ </sup>cells. Therefore, it is unlikely that the observed T-lineage commitment from HSC is mediated by DLL expressed on keratinocytes. In addition, we did confirm expression of the Notch-ligand Jagged-1 by keratinocytes.</p> <p>Conclusions</p> <p>Currently, and unfortunately, it remains difficult to explain the development or growth of T-cells described by Clark <it>et al.</it>, but for the fate of patients suffering from lymphopenia it is essential to both reproduce and understand how these co-cultures really "work". Fortunately, alternative procedures to speed-up T-cell reconstitution are being established and validated and may become available for patients in the near future.</p> |
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format | Article |
id | doaj.art-d7b2d480bf014460bc263ac33b3a926d |
institution | Directory Open Access Journal |
issn | 1471-2172 |
language | English |
last_indexed | 2024-12-11T20:43:40Z |
publishDate | 2011-02-01 |
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series | BMC Immunology |
spelling | doaj.art-d7b2d480bf014460bc263ac33b3a926d2022-12-22T00:51:26ZengBMCBMC Immunology1471-21722011-02-011211710.1186/1471-2172-12-17T cells fail to develop in the human skin-cell explants system; an inconvenient truthVanderlocht JorisLumeij Stijn BJTonnaer Siebevan der Stegen Sjoukje JCHuijskens Mirelle JAJVan Elssen Catharina HMJMeek BobKirkland Mark AHesselink ReinoutGermeraad Wilfred TVBos Gerard MJ<p>Abstract</p> <p>Background</p> <p>Haplo-identical hematopoietic stem cell (HSC) transplantation is very successful in eradicating haematological tumours, but the long post-transplant T-lymphopenic phase is responsible for high morbidity and mortality rates. Clark <it>et al. </it>have described a skin-explant system capable of producing host-tolerant donor-HSC derived T-cells. Because this T-cell production platform has the potential to replenish the T-cell levels following transplantation, we set out to validate the skin-explant system.</p> <p>Results</p> <p>Following the published procedures, while using the same commercial components, it was impossible to reproduce the skin-explant conditions required for HSC differentiation towards mature T-cells. The keratinocyte maturation procedure resulted in fragile cells with minimum expression of delta-like ligand (DLL). In most experiments the generated cells failed to adhere to carriers or were quickly outcompeted by fibroblasts. Consequently it was not possible to reproduce cell-culture conditions required for HSC differentiation into functional T-cells. Using cell-lines over-expressing DLL, we showed that the antibodies used by Clark <it>et al. </it>were unable to detect native DLL, but instead stained 7AAD<sup>+ </sup>cells. Therefore, it is unlikely that the observed T-lineage commitment from HSC is mediated by DLL expressed on keratinocytes. In addition, we did confirm expression of the Notch-ligand Jagged-1 by keratinocytes.</p> <p>Conclusions</p> <p>Currently, and unfortunately, it remains difficult to explain the development or growth of T-cells described by Clark <it>et al.</it>, but for the fate of patients suffering from lymphopenia it is essential to both reproduce and understand how these co-cultures really "work". Fortunately, alternative procedures to speed-up T-cell reconstitution are being established and validated and may become available for patients in the near future.</p>http://www.biomedcentral.com/1471-2172/12/17 |
spellingShingle | Vanderlocht Joris Lumeij Stijn BJ Tonnaer Siebe van der Stegen Sjoukje JC Huijskens Mirelle JAJ Van Elssen Catharina HMJ Meek Bob Kirkland Mark A Hesselink Reinout Germeraad Wilfred TV Bos Gerard MJ T cells fail to develop in the human skin-cell explants system; an inconvenient truth BMC Immunology |
title | T cells fail to develop in the human skin-cell explants system; an inconvenient truth |
title_full | T cells fail to develop in the human skin-cell explants system; an inconvenient truth |
title_fullStr | T cells fail to develop in the human skin-cell explants system; an inconvenient truth |
title_full_unstemmed | T cells fail to develop in the human skin-cell explants system; an inconvenient truth |
title_short | T cells fail to develop in the human skin-cell explants system; an inconvenient truth |
title_sort | t cells fail to develop in the human skin cell explants system an inconvenient truth |
url | http://www.biomedcentral.com/1471-2172/12/17 |
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