In vitro susceptibility of CD4+ and CD8+ T cell subsets to fludarabine

Autores
Gamberale, Romina; Galmarini, Carlos Maria; Fernández Calotti, Paula; Jordheim, Lars; Sánchez Ávalos, Julio César Américo; Dumontet, Charles; Geffner, Jorge Raúl; Giordano, Mirta Nilda
Año de publicación
2003
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Administration of the adenosine analogue fludarabine (FLU) in vivo induces a profound and prolonged T lymphopenia which mainly affects CD4+ cells. To better understand the mechanistic basis underlying this preferential depletion, we analyzed the in vitro susceptibility of T cell subsets to FLU-induced apoptosis. Contrasting with observations in vivo, our results showed that treatment of peripheral blood mononuclear cells with FLU induced a higher level of apoptosis in CD8+ than in CD4+ T lymphocytes. This increased sensitivity of CD8+ T cells to FLU was observed in samples from both, healthy donors and B cell chronic lymphocytic leukemia patients, and resulted in higher CD4:CD8 ratios in FLU-treated than in untreated cultures (P<0.01). Expression of factors involved in FLU transport and metabolism was then evaluated by quantitative real time-PCR in normal T cell subsets. It was found that mRNA levels of human equilibrative nucleoside transporter-1 nucleoside transporter were higher whereas deoxycytidine kinase and IMP/GMP selective 5′-nucleotidase mRNA levels were lower in CD4 + cells. However the dCK/cN-II ratio was 2-fold greater in CD8 + than in CD4+ T lymphocytes, which could account for the higher apoptosis levels observed in the CD8+ subset. These results favor the view that decreased CD4:CD8 ratios in FLU-treated patients should be attributed to differences in cell recovery and/or homing between T cell subsets. © 2003 Elsevier Inc. All rights reserved.
Fil: Gamberale, Romina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Invest. Hematologicas "Mariano R. Castex". Departamento de Inmunologia y Medicina Experimental. Div.de Inmunologia Oncologica; Argentina
Fil: Galmarini, Carlos Maria. Faculté de Médécine Rockefeller; Francia
Fil: Fernández Calotti, Paula. Academia Nacional de Medicina de Buenos Aires. Instituto de Invest. Hematologicas "Mariano R. Castex". Departamento de Inmunologia y Medicina Experimental. Div.de Inmunologia Oncologica; Argentina
Fil: Jordheim, Lars. Faculté de Médécine Rockefeller; Francia
Fil: Sánchez Ávalos, Julio César Américo. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina
Fil: Dumontet, Charles. Faculté de Médécine Rockefeller; Francia
Fil: Geffner, Jorge Raúl. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Invest. Hematologicas "Mariano R. Castex". Departamento de Inmunologia y Medicina Experimental. Div.de Inmunologia Oncologica; Argentina
Fil: Giordano, Mirta Nilda. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Invest. Hematologicas "Mariano R. Castex". Departamento de Inmunologia y Medicina Experimental. Div.de Inmunologia Oncologica; Argentina
Materia
Apoptosis
Fludarabine
Leukemia
Purine Nucleosides
T Lymphocyte Subsets
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/66367
Acceder
id CONICETDig_1233acc20199b64263dfa4aa78cda83c
oai_identifier_str oai:ri.conicet.gov.ar:11336/66367
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling In vitro susceptibility of CD4+ and CD8+ T cell subsets to fludarabineGamberale, RominaGalmarini, Carlos MariaFernández Calotti, PaulaJordheim, LarsSánchez Ávalos, Julio César AméricoDumontet, CharlesGeffner, Jorge RaúlGiordano, Mirta NildaApoptosisFludarabineLeukemiaPurine NucleosidesT Lymphocyte Subsetshttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3Administration of the adenosine analogue fludarabine (FLU) in vivo induces a profound and prolonged T lymphopenia which mainly affects CD4+ cells. To better understand the mechanistic basis underlying this preferential depletion, we analyzed the in vitro susceptibility of T cell subsets to FLU-induced apoptosis. Contrasting with observations in vivo, our results showed that treatment of peripheral blood mononuclear cells with FLU induced a higher level of apoptosis in CD8+ than in CD4+ T lymphocytes. This increased sensitivity of CD8+ T cells to FLU was observed in samples from both, healthy donors and B cell chronic lymphocytic leukemia patients, and resulted in higher CD4:CD8 ratios in FLU-treated than in untreated cultures (P<0.01). Expression of factors involved in FLU transport and metabolism was then evaluated by quantitative real time-PCR in normal T cell subsets. It was found that mRNA levels of human equilibrative nucleoside transporter-1 nucleoside transporter were higher whereas deoxycytidine kinase and IMP/GMP selective 5′-nucleotidase mRNA levels were lower in CD4 + cells. However the dCK/cN-II ratio was 2-fold greater in CD8 + than in CD4+ T lymphocytes, which could account for the higher apoptosis levels observed in the CD8+ subset. These results favor the view that decreased CD4:CD8 ratios in FLU-treated patients should be attributed to differences in cell recovery and/or homing between T cell subsets. © 2003 Elsevier Inc. All rights reserved.Fil: Gamberale, Romina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Invest. Hematologicas "Mariano R. Castex". Departamento de Inmunologia y Medicina Experimental. Div.de Inmunologia Oncologica; ArgentinaFil: Galmarini, Carlos Maria. Faculté de Médécine Rockefeller; FranciaFil: Fernández Calotti, Paula. Academia Nacional de Medicina de Buenos Aires. Instituto de Invest. Hematologicas "Mariano R. Castex". Departamento de Inmunologia y Medicina Experimental. Div.de Inmunologia Oncologica; ArgentinaFil: Jordheim, Lars. Faculté de Médécine Rockefeller; FranciaFil: Sánchez Ávalos, Julio César Américo. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Dumontet, Charles. Faculté de Médécine Rockefeller; FranciaFil: Geffner, Jorge Raúl. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Invest. Hematologicas "Mariano R. Castex". Departamento de Inmunologia y Medicina Experimental. Div.de Inmunologia Oncologica; ArgentinaFil: Giordano, Mirta Nilda. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Invest. Hematologicas "Mariano R. Castex". Departamento de Inmunologia y Medicina Experimental. Div.de Inmunologia Oncologica; ArgentinaPergamon-Elsevier Science Ltd2003-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/66367Gamberale, Romina; Galmarini, Carlos Maria; Fernández Calotti, Paula; Jordheim, Lars; Sánchez Ávalos, Julio César Américo; et al.; In vitro susceptibility of CD4+ and CD8+ T cell subsets to fludarabine; Pergamon-Elsevier Science Ltd; Biochemical Pharmacology; 66; 11; 12-2003; 2185-21910006-2952CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.bcp.2003.07.008info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0006295203006208info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:18:33Zoai:ri.conicet.gov.ar:11336/66367instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:18:33.436CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv In vitro susceptibility of CD4+ and CD8+ T cell subsets to fludarabine
title In vitro susceptibility of CD4+ and CD8+ T cell subsets to fludarabine
spellingShingle In vitro susceptibility of CD4+ and CD8+ T cell subsets to fludarabine
Gamberale, Romina
Apoptosis
Fludarabine
Leukemia
Purine Nucleosides
T Lymphocyte Subsets
title_short In vitro susceptibility of CD4+ and CD8+ T cell subsets to fludarabine
title_full In vitro susceptibility of CD4+ and CD8+ T cell subsets to fludarabine
title_fullStr In vitro susceptibility of CD4+ and CD8+ T cell subsets to fludarabine
title_full_unstemmed In vitro susceptibility of CD4+ and CD8+ T cell subsets to fludarabine
title_sort In vitro susceptibility of CD4+ and CD8+ T cell subsets to fludarabine
dc.creator.none.fl_str_mv Gamberale, Romina
Galmarini, Carlos Maria
Fernández Calotti, Paula
Jordheim, Lars
Sánchez Ávalos, Julio César Américo
Dumontet, Charles
Geffner, Jorge Raúl
Giordano, Mirta Nilda
author Gamberale, Romina
author_facet Gamberale, Romina
Galmarini, Carlos Maria
Fernández Calotti, Paula
Jordheim, Lars
Sánchez Ávalos, Julio César Américo
Dumontet, Charles
Geffner, Jorge Raúl
Giordano, Mirta Nilda
author_role author
author2 Galmarini, Carlos Maria
Fernández Calotti, Paula
Jordheim, Lars
Sánchez Ávalos, Julio César Américo
Dumontet, Charles
Geffner, Jorge Raúl
Giordano, Mirta Nilda
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Apoptosis
Fludarabine
Leukemia
Purine Nucleosides
T Lymphocyte Subsets
topic Apoptosis
Fludarabine
Leukemia
Purine Nucleosides
T Lymphocyte Subsets
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Administration of the adenosine analogue fludarabine (FLU) in vivo induces a profound and prolonged T lymphopenia which mainly affects CD4+ cells. To better understand the mechanistic basis underlying this preferential depletion, we analyzed the in vitro susceptibility of T cell subsets to FLU-induced apoptosis. Contrasting with observations in vivo, our results showed that treatment of peripheral blood mononuclear cells with FLU induced a higher level of apoptosis in CD8+ than in CD4+ T lymphocytes. This increased sensitivity of CD8+ T cells to FLU was observed in samples from both, healthy donors and B cell chronic lymphocytic leukemia patients, and resulted in higher CD4:CD8 ratios in FLU-treated than in untreated cultures (P<0.01). Expression of factors involved in FLU transport and metabolism was then evaluated by quantitative real time-PCR in normal T cell subsets. It was found that mRNA levels of human equilibrative nucleoside transporter-1 nucleoside transporter were higher whereas deoxycytidine kinase and IMP/GMP selective 5′-nucleotidase mRNA levels were lower in CD4 + cells. However the dCK/cN-II ratio was 2-fold greater in CD8 + than in CD4+ T lymphocytes, which could account for the higher apoptosis levels observed in the CD8+ subset. These results favor the view that decreased CD4:CD8 ratios in FLU-treated patients should be attributed to differences in cell recovery and/or homing between T cell subsets. © 2003 Elsevier Inc. All rights reserved.
Fil: Gamberale, Romina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Invest. Hematologicas "Mariano R. Castex". Departamento de Inmunologia y Medicina Experimental. Div.de Inmunologia Oncologica; Argentina
Fil: Galmarini, Carlos Maria. Faculté de Médécine Rockefeller; Francia
Fil: Fernández Calotti, Paula. Academia Nacional de Medicina de Buenos Aires. Instituto de Invest. Hematologicas "Mariano R. Castex". Departamento de Inmunologia y Medicina Experimental. Div.de Inmunologia Oncologica; Argentina
Fil: Jordheim, Lars. Faculté de Médécine Rockefeller; Francia
Fil: Sánchez Ávalos, Julio César Américo. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina
Fil: Dumontet, Charles. Faculté de Médécine Rockefeller; Francia
Fil: Geffner, Jorge Raúl. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Invest. Hematologicas "Mariano R. Castex". Departamento de Inmunologia y Medicina Experimental. Div.de Inmunologia Oncologica; Argentina
Fil: Giordano, Mirta Nilda. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Invest. Hematologicas "Mariano R. Castex". Departamento de Inmunologia y Medicina Experimental. Div.de Inmunologia Oncologica; Argentina
description Administration of the adenosine analogue fludarabine (FLU) in vivo induces a profound and prolonged T lymphopenia which mainly affects CD4+ cells. To better understand the mechanistic basis underlying this preferential depletion, we analyzed the in vitro susceptibility of T cell subsets to FLU-induced apoptosis. Contrasting with observations in vivo, our results showed that treatment of peripheral blood mononuclear cells with FLU induced a higher level of apoptosis in CD8+ than in CD4+ T lymphocytes. This increased sensitivity of CD8+ T cells to FLU was observed in samples from both, healthy donors and B cell chronic lymphocytic leukemia patients, and resulted in higher CD4:CD8 ratios in FLU-treated than in untreated cultures (P<0.01). Expression of factors involved in FLU transport and metabolism was then evaluated by quantitative real time-PCR in normal T cell subsets. It was found that mRNA levels of human equilibrative nucleoside transporter-1 nucleoside transporter were higher whereas deoxycytidine kinase and IMP/GMP selective 5′-nucleotidase mRNA levels were lower in CD4 + cells. However the dCK/cN-II ratio was 2-fold greater in CD8 + than in CD4+ T lymphocytes, which could account for the higher apoptosis levels observed in the CD8+ subset. These results favor the view that decreased CD4:CD8 ratios in FLU-treated patients should be attributed to differences in cell recovery and/or homing between T cell subsets. © 2003 Elsevier Inc. All rights reserved.
publishDate 2003
dc.date.none.fl_str_mv 2003-12
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/66367
Gamberale, Romina; Galmarini, Carlos Maria; Fernández Calotti, Paula; Jordheim, Lars; Sánchez Ávalos, Julio César Américo; et al.; In vitro susceptibility of CD4+ and CD8+ T cell subsets to fludarabine; Pergamon-Elsevier Science Ltd; Biochemical Pharmacology; 66; 11; 12-2003; 2185-2191
0006-2952
CONICET Digital
CONICET
url http://hdl.handle.net/11336/66367
identifier_str_mv Gamberale, Romina; Galmarini, Carlos Maria; Fernández Calotti, Paula; Jordheim, Lars; Sánchez Ávalos, Julio César Américo; et al.; In vitro susceptibility of CD4+ and CD8+ T cell subsets to fludarabine; Pergamon-Elsevier Science Ltd; Biochemical Pharmacology; 66; 11; 12-2003; 2185-2191
0006-2952
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.bcp.2003.07.008
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0006295203006208
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Pergamon-Elsevier Science Ltd
publisher.none.fl_str_mv Pergamon-Elsevier Science Ltd
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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