Calcineurin and mTOR inhibitors have opposing effects on regulatory T cells while reducing regulatory B cell populations in kidney transplant recipients

• Regulatory B cells increase over time after transplantation, suggesting that they might be related with graft survival.
• Immunosuppressive drugs have a differential effect on regulatory lymphocyte subsets.
• KT recipients under CNI treatment show reduced levels of regulatory B and T cells.
• KT recipients under mTOR treatment show reduced levels of regulatory B cells while regulatory T cells numbers are maintained.

BackgroundRegulatory B (Breg) and T (Treg) cells represent a biomarker for tolerance in transplant patients. Despite the importance of Treg and Breg in transplantation and the suggested crosstalk between both suppressive cell populations, little is known on how they are influenced by long-term immunosuppressive treatment. The aim of the present study was to investigate the effect of different immunosuppressive drugs used in routine clinical practice on Treg and Breg cell numbers.MethodsThirty-six kidney transplant recipients with stable graft function were recruited and classified according to their concomitant therapy: 22 patients received calcineurin inhibitors (CNI) and 14 patients received mammalian target of rapamycin (mTOR) inhibitors. A group of 8 healthy untreated subjects was included as control. Absolute numbers of peripheral blood-derived IL10-producing B cells (CD19+IL10+), CD19+CD24hiCD38hi transitional B cells and Treg cells (CD4+CD25+FOXP3+) were quantified in all KT patients and controls by flow cytometry.ResultsCD19+CD24hiCD38hi transitional B cells increased over time and seem to be related with long-term therapeutic graft survival irrespective of the treatment regimen. CNI and mTOR inhibitors significantly reduced numbers of Breg cells when compared with healthy individuals, whereas mTOR inhibitors expanded Treg cells in comparison with CNI drugs.ConclusionsBridging the drug-mediated reduction of Breg cell numbers in vivo with the requirements of Breg cells for long-term transplant success remains an as yet unresolved task for therapeutic intervention. Further larger cohort studies that evaluate the effect of different treatment regimen on defined lymphocyte subpopulations are warranted.