1. In vitro effects of cyclosporine A and tacrolimus on regulatory T-cell proliferation and function
- Author
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Olivier Moralès, Nadira Delhem, Yvan de Launoit, Véronique Pancré, Céline Miroux, Filomena Conti, Khaldoun Ghazal, Samia Ben Othman, Institut de biologie de Lille - IBL (IBLI), Université de Lille, Sciences et Technologies-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie de Lille, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Biologie Cellulaire, Université Paris Descartes - Paris 5 (UPD5), Unité de Transplantation, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de biologie de Lille - IBL ( IBLI ), Réseau International des Instituts Pasteur ( RIIP ) -Réseau International des Instituts Pasteur ( RIIP ) -Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique ( CNRS ), Réseau International des Instituts Pasteur ( RIIP ) -Réseau International des Instituts Pasteur ( RIIP ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de Recherche Saint-Antoine ( CR Saint-Antoine ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris Descartes - Paris 5 ( UPD5 ), CHU Cochin [AP-HP], Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre National de la Recherche Scientifique (CNRS)-Université de Lille, Droit et Santé, Mécanismes de tumorigenèse et thérapies ciblées, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), and Centre de Recherche Saint-Antoine (CR Saint-Antoine)
- Subjects
medicine.medical_treatment ,MESH : Cytokines ,Pharmacology ,Lymphocyte Activation ,T-Lymphocytes, Regulatory ,MESH: Cyclosporine ,chemistry.chemical_compound ,MESH : Phosphorylation ,MESH : T-Lymphocytes, Regulatory ,0302 clinical medicine ,[ SDV.IMM ] Life Sciences [q-bio]/Immunology ,Phosphorylation ,MESH : Immunosuppressive Agents ,Cells, Cultured ,ComputingMilieux_MISCELLANEOUS ,0303 health sciences ,MESH: Cytokines ,hemic and immune systems ,3. Good health ,Cytokine ,medicine.anatomical_structure ,MESH : Calcineurin ,030220 oncology & carcinogenesis ,MESH : Immunophenotyping ,Cyclosporine ,Cytokines ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,MESH: Calcineurin ,MESH: Immunosuppressive Agents ,Immunosuppressive Agents ,medicine.drug ,MESH: Cells, Cultured ,Interleukin 2 ,MESH: Liver Transplantation ,MESH: Immunophenotyping ,Regulatory T cell ,T cell ,Calcineurin Inhibitors ,NIM811 ,MESH: NFATC Transcription Factors ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,chemical and pharmacologic phenomena ,Biology ,Tacrolimus ,Immunophenotyping ,Proinflammatory cytokine ,03 medical and health sciences ,MESH : Cyclosporine ,MESH : Cells, Cultured ,medicine ,MESH: Tacrolimus ,Humans ,MESH: Lymphocyte Activation ,MESH : Lymphocyte Activation ,030304 developmental biology ,Transplantation ,MESH: Humans ,NFATC Transcription Factors ,MESH: Phosphorylation ,MESH : NFATC Transcription Factors ,MESH: T-Lymphocytes, Regulatory ,MESH : Humans ,MESH : Tacrolimus ,Liver Transplantation ,Calcineurin ,chemistry ,Immunology ,MESH : Liver Transplantation - Abstract
International audience; BACKGROUND: Liver transplantation is the treatment of end-stage liver diseases, including hepatitis C. Immunosuppression prevents graft rejection but seems to accelerate the recurrence of hepatitis C. Regulatory T cells (Tregs) may be beneficial in tolerance but deleterious in recurrent hepatitis C. We evaluated the effects of cyclosporine or tacrolimus, the principal immunosuppressive drugs, on Treg proliferation and function. METHODS: Human Tregs were isolated from healthy donors and cultured with cyclosporine, tacrolimus, or NIM811, a cyclosporine analog devoid of calcineurin-inhibiting activity. Treg proliferation and suppressive activity were assessed. The phenotype, cytokine production, and phosphorylation profile of nuclear factor of activated T cell of Tregs were also analyzed. RESULTS: Cyclosporine and tacrolimus both decreased Treg proliferation, but only low doses of cyclosporine reduced Treg activity, by inducing the production of interleukin 2 proinflammatory cytokines in these cells. Moreover, NIM811 also inhibited Treg activity. The phosphorylation of nuclear factor of activated T cell in Tregs was not altered by cyclosporine, suggesting that the effects of this drug are independent of the calcineurin pathway. CONCLUSION: In summary, low doses of cyclosporine inhibit Treg activity, a finding that might explain the beneficial effect of this drug on hepatitis C recurrence. In contrast, by maintaining Treg activity, tacrolimus could be more helpful than cyclosporine in controlling rejection.
- Published
- 2012
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