title: Different in vitro proliferation and cytokine-production inhibition of memory T-cell subsets after calcineurin and mammalian target of rapamycin inhibitors treatment.
abstract: Calcineurin inhibitors (CNI) and mammalian target of rapamycin inhibitors (mTORi) are the main immunosuppressants used for long-term maintenance therapy in transplant recipients to avoid acute rejection episodes. Both groups of immunosuppressants have wide effects and are focused against the T cells, although different impacts on specific T-cell subsets, such as regulatory T cells, have been demonstrated. A greater knowledge of the impact of immunosuppression on the cellular components involved in allograft rejection could facilitate decisions for individualized immunosuppression when an acute rejection event is suspected. Memory T cells have recently gained focus because they might induce a more potent response compared with naive cells. The impact of immunosuppressants on different memory T-cell subsets remains unclear. In the present study, we have studied the specific impact of CNI (tacrolimus) and mTORi (rapamycin and everolimus) over memory and naive CD4(+) T cells. To do so, we have analysed the proliferation, phenotypic changes and cytokine synthesis in vitro in the presence of these immunosuppressants. The present work shows a more potent effect of CNI on proliferation and cytokine production in naive and memory T cells. However, the mTORi permit the differentiation of naive T cells to the memory phenotype and allow the production of interleukin-2. Taken together, our data show evidence to support the combined use of CNI and mTORi in transplant immunosuppression.
authors.affiliation: Autoimmunity and Transplant Group-IDIVAL, Santander, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Merino
authors.affiliation: Immunology Service Hospital Universitario Marqués de Valdecilla-IDIVAL, Santander, Spain.
authors.forename: David
authors.initials: D
authors.lastname: San Segundo
authors.affiliation: Autoimmunity and Transplant Group-IDIVAL, Santander, Spain.
authors.forename: Juan M
authors.initials: JM
authors.lastname: Medina
authors.affiliation: Nephrology Service Hospital Universitario Marqués de Valdecilla-IDIVAL, Santander, Spain.
authors.forename: Emilio
authors.initials: E
authors.lastname: Rodrigo
authors.affiliation: Immunology Service Hospital Universitario Marqués de Valdecilla-IDIVAL, Santander, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Asensio
authors.affiliation: Immunology Service Hospital Universitario Marqués de Valdecilla-IDIVAL, Santander, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Irure
authors.affiliation: Nephrology Service Hospital Universitario Marqués de Valdecilla-IDIVAL, Santander, Spain.
authors.forename: Gema
authors.initials: G
authors.lastname: Fernández-Fresnedo
authors.affiliation: Nephrology Service Hospital Universitario Marqués de Valdecilla-IDIVAL, Santander, Spain.
authors.forename: Manuel A
authors.initials: MA
authors.lastname: Arias
authors.affiliation: Immunology Service Hospital Universitario Marqués de Valdecilla-IDIVAL, Santander, Spain.
authors.forename: Marcos
authors.initials: M
authors.lastname: López-Hoyos
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D065095:Calcineurin Inhibitors / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D000068338:Everolimus / Q000494:pharmacology; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D016377:Organ Transplantation; D020123:Sirolimus / Q000494:pharmacology; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D016559:Tacrolimus / Q000494:pharmacology
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D000068338:Everolimus; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus; D016559:Tacrolimus
keywords: T cells; cell differentiation; cell proliferation; cytokines; transplantation