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
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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