Abstract
Kidney transplantation is currently the first choice of treatment for various types of end-stage renal failure, but there are major limitations in the application of immunosuppressive protocols after kidney transplantation. When the dose of immunosuppressant is too low, graft rejection occurs easily, while a dose that is too high can lead to graft loss. Therefore, it is very important to explore the immune status of patients receiving immunosuppressive agents after kidney transplantation. To compare the immune status of the recipient’s whole peripheral blood before and after receipt of immunosuppressive agents, we used single-cell cytometry by time-of-flight (CyTOF) to detect the peripheral blood immune cells in five kidney transplant recipients (KTRs) from the Department of Organ Transplantation of Zhujiang Hospital of Southern Medical University before and after receiving immunosuppressive agents. Based on CyTOF analysis, we detected 363,342 live single immune cells. We found that the immune cell types of the KTRs before and after receipt of immunosuppressive agents were mainly divided into CD4+ T cells, CD8+ T cells, B cells, NK cells/γδ T cells, monocytes/macrophages, granulocytes, and dendritic cells (DCs). After further reclustering of the above cell types, it was found that the immune cell subclusters in the peripheral blood of patients underwent major changes after receipt of immunosuppressants. After receiving immunosuppressive therapy, the peripheral blood of KTRs had significantly increased levels of CD57+NK cells and significantly decreased levels of central memory CD4+ T cells, follicular helper CD4+ T cells, effector CD8+ T cells, effector memory CD8+ T cells and naive CD8+ T cells. This study used CyTOF to classify immune cells in the peripheral blood of KTRs before and after immunosuppressive treatment, further compared differences in the proportions of the main immune cell types and immune cell subgroups before and after receipt of immunosuppressants, and provided relatively accurate information for assessment and treatment strategies for KTRs.
Highlights
Kidney transplantation is currently recognized by the international medical community as the first choice of treatment for various types of end-stage renal failure [1, 2]
CD45+ cells was performed with various markers, such as those for CD4+ T cells, CD8+ T cells, B cells, NK cells/gd T cells, monocytes/macrophages, granulocytes, and dendritic cells (DCs; markers: CD11c and CD123) (Figure 1A)
We compared the relative abundances of immune cells in the peripheral blood of kidney transplant recipients (KTRs) between the pretreatment and posttreatment groups (Figure 1D) and found that, compared with the pretreatment group, the relative abundance of CD4+ T cells in the posttreatment group was significantly downregulated (P
Summary
Kidney transplantation is currently recognized by the international medical community as the first choice of treatment for various types of end-stage renal failure [1, 2]. Optimized immunosuppressive regimens and new immune detection technologies have significantly improved the shortterm outcomes of transplant recipients after surgery, but effective methods for immune system function monitoring in patients after kidney transplantation are still lacking, leading to many blind spots in the clinical application of immunosuppressive agents. When the dose of immunosuppressant is too low, graft rejection can occur, and improper handling can lead to loss of the graft. Too high a dose of immunosuppressant can impair the patient’s immune system, making them prone to bacterial infection. Infections with fungi, viruses, and protozoa have become the most important causes of death in transplant patients [1,2,3]. It is important to explore the immune status of patients receiving immunosuppressive agents after kidney transplantation
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