Relationship of transitional regulatory B and regulatory T cells and immunosuppressive drug doses in stable renal transplant recipients.

Autor: Ibrahim EH; Transplantation Immunology, Institute of Immunology, University Hospital Heidelberg, Heidelberg, Germany.; Clinical Pathology Department, South Egypt Cancer Institute, Assiut University, Assiut, Egypt., Aly M; Transplantation Immunology, Institute of Immunology, University Hospital Heidelberg, Heidelberg, Germany.; Department of Nephrology, University Hospital Heidelberg, Heidelberg, Germany.; Nephrology Unit, Internal Medicine Department, Assiut University, Assiut, Egypt., Morath C; Department of Nephrology, University Hospital Heidelberg, Heidelberg, Germany., Sayed DM; Clinical Pathology Department, South Egypt Cancer Institute, Assiut University, Assiut, Egypt., Ekpoom N; Transplantation Immunology, Institute of Immunology, University Hospital Heidelberg, Heidelberg, Germany., Opelz G; Transplantation Immunology, Institute of Immunology, University Hospital Heidelberg, Heidelberg, Germany., Süsal C; Transplantation Immunology, Institute of Immunology, University Hospital Heidelberg, Heidelberg, Germany., Daniel V; Transplantation Immunology, Institute of Immunology, University Hospital Heidelberg, Heidelberg, Germany.
Jazyk: angličtina
Zdroj: Immunity, inflammation and disease [Immun Inflamm Dis] 2021 Dec; Vol. 9 (4), pp. 1252-1271. Date of Electronic Publication: 2021 Jun 08.
DOI: 10.1002/iid3.473
Abstrakt: Objectives: Regulatory B cells (Bregs) and T cells (Tregs) are thought to be involved in the regulation of graft acceptance in renal transplant recipients. However, mechanisms that affect Breg differentiation and interaction with Tregs are rather unclear.
Methods: Using eight-color-fluorescence flow cytometry, Tregs and CD19+ CD24hiCD38hi Bregs were analyzed in whole blood samples of 80 stable kidney transplant recipients, 20 end-stage renal disease (ESRD) patients and 32 healthy controls (HC). In addition, differentiation of Bregs and Tregs was studied in different micromilieus using cocultures with strongly enriched B-lymphocytes and autologous peripheral blood mononuclear cells stimulated with CpG and phytohemagglutinin.
Results: Bregs were higher in HC than in ESRD patients and lowest in transplant recipients. Bregs were higher early as compared to late posttransplant. Posttransplant, high Bregs were associated with higher glomerular filtration rate (GFR) and lower C-reactive protein (CRP). Higher doses and blood levels of ciclosporine, tacrolimus, and mycophenolate mofetil as well as higher doses of steroids were not associated with low Bregs. In contrast, most Treg subsets were lower when blood levels of ciclosporine, tacrolimus, and mycophenolate mofetil were higher. Tregs were not associated with Bregs, GFR, CRP plasma levels, and occurrence of rejection or infection. In vitro, differentiation of Bregs was strongly dependent on T cell support and was blocked by excessive or lacking T-cell help. Tregs were not associated with Breg numbers in vitro.
Conclusion: Bregs appear to be insensitive to high doses of posttransplant immunosuppressive drugs. The protracted Breg decrease posttransplant might be caused by impaired T cell support attributable to immunosuppressive drugs.
(© 2021 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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