Human FOXN1-deficiency is associated with αβ double-negative and FoxP3+ T-cell expansions that are distinctly modulated upon thymic transplantation

Detalhes bibliográficos
Autor(a) principal: Albuquerque, A. S.
Data de Publicação: 2002
Outros Autores: Marques, J. G., Silva, S. L., Ligeiro, D., Devlin, B. H., Dutrieux, J., Cheynier, R., Pignata, C., Victorino, R. M., Markert, M. L., Sousa, A. E.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/15877
Resumo: © 2012 Albuquerque et al. 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 credited.
id RCAP_60a27e7e951e822d18765731a5c075c7
oai_identifier_str oai:repositorio.ul.pt:10451/15877
network_acronym_str RCAP
network_name_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository_id_str 7160
spelling Human FOXN1-deficiency is associated with αβ double-negative and FoxP3+ T-cell expansions that are distinctly modulated upon thymic transplantation© 2012 Albuquerque et al. 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 credited.Forkhead box N1 (FOXN1) is a transcription factor crucial for thymic epithelium development and prevention of its involution. Investigation of a patient with a rare homozygous FOXN1 mutation (R255X), leading to alopecia universalis and thymus aplasia, unexpectedly revealed non-maternal circulating T-cells, and, strikingly, large numbers of aberrant doublenegative ab T-cells (CD4negCD8neg, DN) and regulatory-like T-cells. These data raise the possibility that a thymic rudiment persisted, allowing T-cell development, albeit with disturbances in positive/negative selection, as suggested by DN and FoxP3+ cell expansions. Although regulatory-like T-cell numbers normalized following HLA-mismatched thymic transplantation, the abDN subset persisted 5 years post-transplantation. Involution of thymus allograft likely occurred 3 years post-transplantation based on sj/bTREC ratio, which estimates intrathymic precursor T-cell divisions and, consequently, thymic explant output. Nevertheless, functional immune-competence was sustained, providing new insights for the design of immunological reconstitution strategies based on thymic transplantation, with potential applications in other clinical settings.This work was supported by grants from ‘‘Fundação para a Ciência e a Tecnologia’’ (FCT) and by ‘‘Programa Operacional Ciência e Inovação 2010’’ (POCI2010) to RMMV and AES. ASA received a scholarship from FCT. Thymus transplantation performed at the Duke University Medical Center, Durham, USA was financially supported by the Portuguese National Health Services. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Public Library of ScienceRepositório da Universidade de LisboaAlbuquerque, A. S.Marques, J. G.Silva, S. L.Ligeiro, D.Devlin, B. H.Dutrieux, J.Cheynier, R.Pignata, C.Victorino, R. M.Markert, M. L.Sousa, A. E.2015-02-03T16:35:06Z20022002-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/15877engPLoS ONE May 2012 | Volume 7 | Issue 5 | e370421932-6203http://dx.doi.org/ 10.1371/journal.pone.0037042info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T16:02:47Zoai:repositorio.ul.pt:10451/15877Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:37:10.692008Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Human FOXN1-deficiency is associated with αβ double-negative and FoxP3+ T-cell expansions that are distinctly modulated upon thymic transplantation
title Human FOXN1-deficiency is associated with αβ double-negative and FoxP3+ T-cell expansions that are distinctly modulated upon thymic transplantation
spellingShingle Human FOXN1-deficiency is associated with αβ double-negative and FoxP3+ T-cell expansions that are distinctly modulated upon thymic transplantation
Albuquerque, A. S.
title_short Human FOXN1-deficiency is associated with αβ double-negative and FoxP3+ T-cell expansions that are distinctly modulated upon thymic transplantation
title_full Human FOXN1-deficiency is associated with αβ double-negative and FoxP3+ T-cell expansions that are distinctly modulated upon thymic transplantation
title_fullStr Human FOXN1-deficiency is associated with αβ double-negative and FoxP3+ T-cell expansions that are distinctly modulated upon thymic transplantation
title_full_unstemmed Human FOXN1-deficiency is associated with αβ double-negative and FoxP3+ T-cell expansions that are distinctly modulated upon thymic transplantation
title_sort Human FOXN1-deficiency is associated with αβ double-negative and FoxP3+ T-cell expansions that are distinctly modulated upon thymic transplantation
author Albuquerque, A. S.
author_facet Albuquerque, A. S.
Marques, J. G.
Silva, S. L.
Ligeiro, D.
Devlin, B. H.
Dutrieux, J.
Cheynier, R.
Pignata, C.
Victorino, R. M.
Markert, M. L.
Sousa, A. E.
author_role author
author2 Marques, J. G.
Silva, S. L.
Ligeiro, D.
Devlin, B. H.
Dutrieux, J.
Cheynier, R.
Pignata, C.
Victorino, R. M.
Markert, M. L.
Sousa, A. E.
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Albuquerque, A. S.
Marques, J. G.
Silva, S. L.
Ligeiro, D.
Devlin, B. H.
Dutrieux, J.
Cheynier, R.
Pignata, C.
Victorino, R. M.
Markert, M. L.
Sousa, A. E.
description © 2012 Albuquerque et al. 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 credited.
publishDate 2002
dc.date.none.fl_str_mv 2002
2002-01-01T00:00:00Z
2015-02-03T16:35:06Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10451/15877
url http://hdl.handle.net/10451/15877
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv PLoS ONE May 2012 | Volume 7 | Issue 5 | e37042
1932-6203
http://dx.doi.org/ 10.1371/journal.pone.0037042
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv
_version_ 1799134269314957312

Registros relacionados