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Thymocytes may persist and differentiate without any input from bone marrow progenitors
Thymus transplants can correct deficiencies of the thymus epithelium caused by the complete DiGeorge syndrome or FOXN1 mutations. However, thymus transplants were never used to correct T cell–intrinsic deficiencies because it is generally believed that thymocytes have short intrinsic lifespans. This...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3420331/ https://www.ncbi.nlm.nih.gov/pubmed/22778388 http://dx.doi.org/10.1084/jem.20120845 |
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author | Peaudecerf, Laetitia Lemos, Sara Galgano, Alessia Krenn, Gerald Vasseur, Florence Di Santo, James P. Ezine, Sophie Rocha, Benedita |
author_facet | Peaudecerf, Laetitia Lemos, Sara Galgano, Alessia Krenn, Gerald Vasseur, Florence Di Santo, James P. Ezine, Sophie Rocha, Benedita |
author_sort | Peaudecerf, Laetitia |
collection | PubMed |
description | Thymus transplants can correct deficiencies of the thymus epithelium caused by the complete DiGeorge syndrome or FOXN1 mutations. However, thymus transplants were never used to correct T cell–intrinsic deficiencies because it is generally believed that thymocytes have short intrinsic lifespans. This notion is based on thymus transplantation experiments where it was shown that thymus-resident cells were rapidly replaced by progenitors originating in the bone marrow. In contrast, here we show that neonatal thymi transplanted into interleukin 7 receptor–deficient hosts harbor populations with extensive capacity to self-renew, and maintain continuous thymocyte generation and export. These thymus transplants reconstitute the full diversity of peripheral T cell repertoires one month after surgery, which is the earliest time point studied. Moreover, transplantation experiments performed across major histocompatibility barriers show that allogeneic transplanted thymi are not rejected, and allogeneic cells do not induce graft-versus-host disease; transplants induced partial or total protection to infection. These results challenge the current dogma that thymocytes cannot self-renew, and indicate a potential use of neonatal thymus transplants to correct T cell–intrinsic deficiencies. Finally, as found with mature T cells, they show that thymocyte survival is determined by the competition between incoming progenitors and resident cells. |
format | Online Article Text |
id | pubmed-3420331 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-34203312013-01-30 Thymocytes may persist and differentiate without any input from bone marrow progenitors Peaudecerf, Laetitia Lemos, Sara Galgano, Alessia Krenn, Gerald Vasseur, Florence Di Santo, James P. Ezine, Sophie Rocha, Benedita J Exp Med Brief Definitive Report Thymus transplants can correct deficiencies of the thymus epithelium caused by the complete DiGeorge syndrome or FOXN1 mutations. However, thymus transplants were never used to correct T cell–intrinsic deficiencies because it is generally believed that thymocytes have short intrinsic lifespans. This notion is based on thymus transplantation experiments where it was shown that thymus-resident cells were rapidly replaced by progenitors originating in the bone marrow. In contrast, here we show that neonatal thymi transplanted into interleukin 7 receptor–deficient hosts harbor populations with extensive capacity to self-renew, and maintain continuous thymocyte generation and export. These thymus transplants reconstitute the full diversity of peripheral T cell repertoires one month after surgery, which is the earliest time point studied. Moreover, transplantation experiments performed across major histocompatibility barriers show that allogeneic transplanted thymi are not rejected, and allogeneic cells do not induce graft-versus-host disease; transplants induced partial or total protection to infection. These results challenge the current dogma that thymocytes cannot self-renew, and indicate a potential use of neonatal thymus transplants to correct T cell–intrinsic deficiencies. Finally, as found with mature T cells, they show that thymocyte survival is determined by the competition between incoming progenitors and resident cells. The Rockefeller University Press 2012-07-30 /pmc/articles/PMC3420331/ /pubmed/22778388 http://dx.doi.org/10.1084/jem.20120845 Text en © 2012 Peaudecerf et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Brief Definitive Report Peaudecerf, Laetitia Lemos, Sara Galgano, Alessia Krenn, Gerald Vasseur, Florence Di Santo, James P. Ezine, Sophie Rocha, Benedita Thymocytes may persist and differentiate without any input from bone marrow progenitors |
title | Thymocytes may persist and differentiate without any input from bone marrow progenitors |
title_full | Thymocytes may persist and differentiate without any input from bone marrow progenitors |
title_fullStr | Thymocytes may persist and differentiate without any input from bone marrow progenitors |
title_full_unstemmed | Thymocytes may persist and differentiate without any input from bone marrow progenitors |
title_short | Thymocytes may persist and differentiate without any input from bone marrow progenitors |
title_sort | thymocytes may persist and differentiate without any input from bone marrow progenitors |
topic | Brief Definitive Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3420331/ https://www.ncbi.nlm.nih.gov/pubmed/22778388 http://dx.doi.org/10.1084/jem.20120845 |
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