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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...

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Autores principales: Peaudecerf, Laetitia, Lemos, Sara, Galgano, Alessia, Krenn, Gerald, Vasseur, Florence, Di Santo, James P., Ezine, Sophie, Rocha, Benedita
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2012
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.
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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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