Fate of lymphocytes after withdrawal of tofacitinib treatment.

Tofacitinib (Tofa) is an inhibitor of Janus Kinase 3, developed for the treatment of autoimmune diseases and for the prevention of transplant rejection. Due to its selective action on proliferating cells, Tofa can offer a way to block T cell activation, without toxic effects on resting cells. Howeve...

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Autores principales:	Elisa Piscianz, Erica Valencic, Eva Cuzzoni, Sara De Iudicibus, Elisa De Lorenzo, Giuliana Decorti, Alberto Tommasini
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c368fa2460f142dba23c19f4c39d15f0
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spelling	oai:doaj.org-article:c368fa2460f142dba23c19f4c39d15f02021-11-18T08:38:08ZFate of lymphocytes after withdrawal of tofacitinib treatment.1932-620310.1371/journal.pone.0085463https://doaj.org/article/c368fa2460f142dba23c19f4c39d15f02014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24416411/?tool=EBIhttps://doaj.org/toc/1932-6203Tofacitinib (Tofa) is an inhibitor of Janus Kinase 3, developed for the treatment of autoimmune diseases and for the prevention of transplant rejection. Due to its selective action on proliferating cells, Tofa can offer a way to block T cell activation, without toxic effects on resting cells. However, few studies have investigated the effects of Tofa on lymphocyte activation in vitro. Our aim was to study the action of Tofa on different lymphocyte subsets after in vitro stimulation and to track the behaviour of treated cells after interruption of the treatment. Peripheral blood lymphocytes were stimulated in vitro with mitogen and treated with two concentrations of Tofa. After a first period in culture, cells were washed and further incubated for an additional time. Lymphocyte subsets, activation phenotype and proliferation were assessed at the different time frames. As expected, Tofa was able to reduce the activation and proliferation of lymphocytes in the first four days of treatment. In addition the drug led to a relative decrease of Natural Killer, B cells and CD8 T cells compared to CD4 T cells. However, treated cells were still viable after the first period in culture and begun to proliferate, strikingly, in a dose dependent manner when the drug was removed from the environment by replacing the culture medium. This novel data does not necessarily predict a similar behaviour in vivo, but can warn about the clinical use of this drug when a discontinuation of treatment with Tofa is considered for any reason.Elisa PiscianzErica ValencicEva CuzzoniSara De IudicibusElisa De LorenzoGiuliana DecortiAlberto TommasiniPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 1, p e85463 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Elisa Piscianz Erica Valencic Eva Cuzzoni Sara De Iudicibus Elisa De Lorenzo Giuliana Decorti Alberto Tommasini Fate of lymphocytes after withdrawal of tofacitinib treatment.
description	Tofacitinib (Tofa) is an inhibitor of Janus Kinase 3, developed for the treatment of autoimmune diseases and for the prevention of transplant rejection. Due to its selective action on proliferating cells, Tofa can offer a way to block T cell activation, without toxic effects on resting cells. However, few studies have investigated the effects of Tofa on lymphocyte activation in vitro. Our aim was to study the action of Tofa on different lymphocyte subsets after in vitro stimulation and to track the behaviour of treated cells after interruption of the treatment. Peripheral blood lymphocytes were stimulated in vitro with mitogen and treated with two concentrations of Tofa. After a first period in culture, cells were washed and further incubated for an additional time. Lymphocyte subsets, activation phenotype and proliferation were assessed at the different time frames. As expected, Tofa was able to reduce the activation and proliferation of lymphocytes in the first four days of treatment. In addition the drug led to a relative decrease of Natural Killer, B cells and CD8 T cells compared to CD4 T cells. However, treated cells were still viable after the first period in culture and begun to proliferate, strikingly, in a dose dependent manner when the drug was removed from the environment by replacing the culture medium. This novel data does not necessarily predict a similar behaviour in vivo, but can warn about the clinical use of this drug when a discontinuation of treatment with Tofa is considered for any reason.
format	article
author	Elisa Piscianz Erica Valencic Eva Cuzzoni Sara De Iudicibus Elisa De Lorenzo Giuliana Decorti Alberto Tommasini
author_facet	Elisa Piscianz Erica Valencic Eva Cuzzoni Sara De Iudicibus Elisa De Lorenzo Giuliana Decorti Alberto Tommasini
author_sort	Elisa Piscianz
title	Fate of lymphocytes after withdrawal of tofacitinib treatment.
title_short	Fate of lymphocytes after withdrawal of tofacitinib treatment.
title_full	Fate of lymphocytes after withdrawal of tofacitinib treatment.
title_fullStr	Fate of lymphocytes after withdrawal of tofacitinib treatment.
title_full_unstemmed	Fate of lymphocytes after withdrawal of tofacitinib treatment.
title_sort	fate of lymphocytes after withdrawal of tofacitinib treatment.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/c368fa2460f142dba23c19f4c39d15f0
work_keys_str_mv	AT elisapiscianz fateoflymphocytesafterwithdrawaloftofacitinibtreatment AT ericavalencic fateoflymphocytesafterwithdrawaloftofacitinibtreatment AT evacuzzoni fateoflymphocytesafterwithdrawaloftofacitinibtreatment AT saradeiudicibus fateoflymphocytesafterwithdrawaloftofacitinibtreatment AT elisadelorenzo fateoflymphocytesafterwithdrawaloftofacitinibtreatment AT giulianadecorti fateoflymphocytesafterwithdrawaloftofacitinibtreatment AT albertotommasini fateoflymphocytesafterwithdrawaloftofacitinibtreatment
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Fate of lymphocytes after withdrawal of tofacitinib treatment.

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