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Thymic output generates a new and diverse TCR repertoire after autologous stem cell transplantation in multiple sclerosis patients

Clinical trials have indicated that autologous hematopoietic stem cell transplantation (HSCT) can persistently suppress inflammatory disease activity in a subset of patients with severe multiple sclerosis (MS), but the mechanism has remained unclear. To understand whether the beneficial effects on t...

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Autores principales: Muraro, Paolo A., Douek, Daniel C., Packer, Amy, Chung, Katherine, Guenaga, Francisco J., Cassiani-Ingoni, Riccardo, Campbell, Catherine, Memon, Sarfraz, Nagle, James W., Hakim, Frances T., Gress, Ronald E., McFarland, Henry F., Burt, Richard K., Martin, Roland
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2005
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2212822/
https://www.ncbi.nlm.nih.gov/pubmed/15738052
http://dx.doi.org/10.1084/jem.20041679
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author Muraro, Paolo A.
Douek, Daniel C.
Packer, Amy
Chung, Katherine
Guenaga, Francisco J.
Cassiani-Ingoni, Riccardo
Campbell, Catherine
Memon, Sarfraz
Nagle, James W.
Hakim, Frances T.
Gress, Ronald E.
McFarland, Henry F.
Burt, Richard K.
Martin, Roland
author_facet Muraro, Paolo A.
Douek, Daniel C.
Packer, Amy
Chung, Katherine
Guenaga, Francisco J.
Cassiani-Ingoni, Riccardo
Campbell, Catherine
Memon, Sarfraz
Nagle, James W.
Hakim, Frances T.
Gress, Ronald E.
McFarland, Henry F.
Burt, Richard K.
Martin, Roland
author_sort Muraro, Paolo A.
collection PubMed
description Clinical trials have indicated that autologous hematopoietic stem cell transplantation (HSCT) can persistently suppress inflammatory disease activity in a subset of patients with severe multiple sclerosis (MS), but the mechanism has remained unclear. To understand whether the beneficial effects on the course of disease are mediated by lympho-depletive effects alone or are sustained by a regeneration of the immune repertoire, we examined the long-term immune reconstitution in patients with MS who received HSCT. After numeric recovery of leukocytes, at 2-yr follow-up there was on average a doubling of the frequency of naive CD4(+) T cells at the expense of memory T cells. Phenotypic and T cell receptor excision circle (TREC) analysis confirmed a recent thymic origin of the expanded naive T cell subset. Analysis of the T cell receptor repertoire showed the reconstitution of an overall broader clonal diversity and an extensive renewal of clonal specificities compared with pretherapy. These data are the first to demonstrate that long-term suppression of inflammatory activity in MS patients who received HSCT does not depend on persisting lymphopenia and is associated with profound qualitative immunological changes that demonstrate a de novo regeneration of the T cell compartment.
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spelling pubmed-22128222008-03-11 Thymic output generates a new and diverse TCR repertoire after autologous stem cell transplantation in multiple sclerosis patients Muraro, Paolo A. Douek, Daniel C. Packer, Amy Chung, Katherine Guenaga, Francisco J. Cassiani-Ingoni, Riccardo Campbell, Catherine Memon, Sarfraz Nagle, James W. Hakim, Frances T. Gress, Ronald E. McFarland, Henry F. Burt, Richard K. Martin, Roland J Exp Med Article Clinical trials have indicated that autologous hematopoietic stem cell transplantation (HSCT) can persistently suppress inflammatory disease activity in a subset of patients with severe multiple sclerosis (MS), but the mechanism has remained unclear. To understand whether the beneficial effects on the course of disease are mediated by lympho-depletive effects alone or are sustained by a regeneration of the immune repertoire, we examined the long-term immune reconstitution in patients with MS who received HSCT. After numeric recovery of leukocytes, at 2-yr follow-up there was on average a doubling of the frequency of naive CD4(+) T cells at the expense of memory T cells. Phenotypic and T cell receptor excision circle (TREC) analysis confirmed a recent thymic origin of the expanded naive T cell subset. Analysis of the T cell receptor repertoire showed the reconstitution of an overall broader clonal diversity and an extensive renewal of clonal specificities compared with pretherapy. These data are the first to demonstrate that long-term suppression of inflammatory activity in MS patients who received HSCT does not depend on persisting lymphopenia and is associated with profound qualitative immunological changes that demonstrate a de novo regeneration of the T cell compartment. The Rockefeller University Press 2005-03-07 /pmc/articles/PMC2212822/ /pubmed/15738052 http://dx.doi.org/10.1084/jem.20041679 Text en Copyright © 2005, The Rockefeller University Press 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 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Muraro, Paolo A.
Douek, Daniel C.
Packer, Amy
Chung, Katherine
Guenaga, Francisco J.
Cassiani-Ingoni, Riccardo
Campbell, Catherine
Memon, Sarfraz
Nagle, James W.
Hakim, Frances T.
Gress, Ronald E.
McFarland, Henry F.
Burt, Richard K.
Martin, Roland
Thymic output generates a new and diverse TCR repertoire after autologous stem cell transplantation in multiple sclerosis patients
title Thymic output generates a new and diverse TCR repertoire after autologous stem cell transplantation in multiple sclerosis patients
title_full Thymic output generates a new and diverse TCR repertoire after autologous stem cell transplantation in multiple sclerosis patients
title_fullStr Thymic output generates a new and diverse TCR repertoire after autologous stem cell transplantation in multiple sclerosis patients
title_full_unstemmed Thymic output generates a new and diverse TCR repertoire after autologous stem cell transplantation in multiple sclerosis patients
title_short Thymic output generates a new and diverse TCR repertoire after autologous stem cell transplantation in multiple sclerosis patients
title_sort thymic output generates a new and diverse tcr repertoire after autologous stem cell transplantation in multiple sclerosis patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2212822/
https://www.ncbi.nlm.nih.gov/pubmed/15738052
http://dx.doi.org/10.1084/jem.20041679
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