Longitudinal analysis of T and B cell phenotype and function in renal transplant recipients with or without rituximab induction therapy.
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.


BACKGROUND
ClinicalTrials.gov NCT00565331.
Department of Laboratory Medicine - Medical Immunology, Radboud University Medical Centre, Nijmegen, The Netherlands.
Elena G
EG
Kamburova
Department of Laboratory Medicine - Medical Immunology, Radboud University Medical Centre, Nijmegen, The Netherlands.
Hans J P M
HJ
Koenen
Department of Nephrology, Radboud University Medical Centre, Nijmegen, The Netherlands.
Martijn W F
MW
van den Hoogen
Department of Nephrology, Radboud University Medical Centre, Nijmegen, The Netherlands.
Marije C
MC
Baas
Department of Laboratory Medicine - Medical Immunology, Radboud University Medical Centre, Nijmegen, The Netherlands.
Irma
I
Joosten
Department of Nephrology, Radboud University Medical Centre, Nijmegen, The Netherlands.
Luuk B
LB
Hilbrands
D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005434:Flow Cytometry; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D006085:Graft Survival / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects; D016130:Immunophenotyping; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007668:Kidney / Q000276:immunology / Q000473:pathology / Q000601:surgery; D016030:Kidney Transplantation; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D010641:Phenotype; D051436:Renal Insufficiency, Chronic / Q000276:immunology / Q000473:pathology / Q000601:surgery; D000069283:Rituximab; D013256:Steroids / Q000627:therapeutic use; D016559:Tacrolimus / Q000627:therapeutic use
D058846:Antibodies, Monoclonal, Murine-Derived; D007166:Immunosuppressive Agents; D013256:Steroids; D000069283:Rituximab; D009173:Mycophenolic Acid; D016559:Tacrolimus