Longitudinal analysis of T and B cell phenotype and function in renal transplant recipients with or without rituximab induction therapy
Autor: | Elena G. Kamburova, Martijn W.F. van den Hoogen, Luuk B. Hilbrands, Hans J. P. M. Koenen, Marije C. Baas, Irma Joosten |
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Rok vydání: | 2014 |
Předmět: |
CD4-Positive T-Lymphocytes
Graft Rejection Male lcsh:Medicine CD8-Positive T-Lymphocytes Kidney Antibodies Monoclonal Murine-Derived Animal Cells Medicine Cytotoxic T cell lcsh:Science Kidney transplantation B-Lymphocytes Multidisciplinary Graft Survival Middle Aged Flow Cytometry medicine.anatomical_structure surgical procedures operative Phenotype Rituximab Drug Therapy Combination Steroids Cellular Types Inflammatory diseases Radboud Institute for Molecular Life Sciences [Radboudumc 5] Immunosuppressive Agents medicine.drug Research Article Adult medicine.medical_specialty Immune Cells Immunology Urology Mycophenolic acid Lymphocyte Depletion Tacrolimus Immunophenotyping Immunomodulation Double-Blind Method Antibody Therapy Transplantation Immunology Humans Kidney surgery Renal Insufficiency Chronic B cell Aged business.industry lcsh:R Biology and Life Sciences Cell Biology Mycophenolic Acid medicine.disease Kidney Transplantation Transplantation lcsh:Q Clinical Immunology Renal disorders Radboud Institute for Health Sciences [Radboudumc 11] business Immunologic Memory |
Zdroj: | PLoS ONE PLoS One, 9, 11 PLoS ONE, Vol 9, Iss 11, p e112658 (2014) PLoS One, 9 |
ISSN: | 1932-6203 |
Popis: | Contains fulltext : 138913.pdf (Publisher’s version ) (Open Access) BACKGROUND: Prevention of rejection after renal transplantation requires treatment with immunosuppressive drugs. Data on their in vivo effects on T- and B-cell phenotype and function are limited. METHODS: In a randomized double-blind placebo-controlled study to prevent renal allograft rejection, patients were treated with tacrolimus, mycophenolate mofetil (MMF), steroids, and a single dose of rituximab or placebo during transplant surgery. In a subset of patients, we analyzed the number and phenotype of peripheral T and B cells by multiparameter flow cytometry before transplantation, and at 3, 6, 12, and 24 months after transplantation. RESULTS: In patients treated with tacrolimus/MMF/steroids the proportion of central memory CD4+ and CD8+ T cells was higher at 3 months post-transplant compared to pre-transplant levels. In addition, the ratio between the percentage of central memory CD4+ and CD4+ regulatory T cells was significantly higher up to 24 months post-transplant compared to pre-transplant levels. Interestingly, treatment with tacrolimus/MMF/steroids resulted in a shift toward a more memory-like B-cell phenotype post-transplant. Addition of a single dose of rituximab resulted in a long-lasting B-cell depletion. At 12 months post-transplant, the small fraction of repopulated B cells consisted of a high percentage of transitional B cells. Rituximab treatment had no effect on the T-cell phenotype and function post-transplant. CONCLUSIONS: Renal transplant recipients treated with tacrolimus/MMF/steroids show an altered memory T and B-cell compartment post-transplant. Additional B-cell depletion by rituximab leads to a relative increase of transitional and memory-like B cells, without affecting T-cell phenotype and function. TRIAL REGISTRATION: ClinicalTrials.gov NCT00565331. |
Databáze: | OpenAIRE |
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