title: Fate of lymphocytes after withdrawal of tofacitinib treatment.
abstract: 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.
authors.affiliation: Department of Diagnostic Medicine, Institute for Maternal and Child Health - IRCCS "Burlo Garofolo", Trieste, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Piscianz
authors.affiliation: Department of Diagnostic Medicine, Institute for Maternal and Child Health - IRCCS "Burlo Garofolo", Trieste, Italy.
authors.forename: Erica
authors.initials: E
authors.lastname: Valencic
authors.affiliation: Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy.
authors.forename: Eva
authors.initials: E
authors.lastname: Cuzzoni
authors.affiliation: Department of Paediatrics, Institute for Maternal and Child Health - IRCCS "Burlo Garofolo", Trieste, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: De Iudicibus
authors.affiliation: Department of Translational Research, National Cancer Institute CRO-IRCCS, Aviano, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: De Lorenzo
authors.affiliation: Department of Life Sciences, University of Trieste, Trieste, Italy.
authors.forename: Giuliana
authors.initials: G
authors.lastname: Decorti
authors.affiliation: Department of Paediatrics, Institute for Maternal and Child Health - IRCCS "Burlo Garofolo", Trieste, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Tommasini
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D049109:Cell Proliferation; D004334:Drug Administration Schedule; D006801:Humans; D053616:Janus Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D008213:Lymphocyte Activation / Q000187:drug effects; D018655:Lymphocyte Count; D010835:Phytohemagglutinins / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology*; D061251:Primary Cell Culture; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology*
chemical_list: D015703:Antigens, CD; D010835:Phytohemagglutinins; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; C479163:tofacitinib; D053616:Janus Kinase 3