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      Immunological Alterations due to Hemodialysis Might Interfere with Early Complications in Renal Transplantation

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          Abstract

          Background

          Chronic or intercurrent alterations of the immune system in patients with end-stage renal disease (CKD) and intermittent hemodialysis (CKD5D, HD) have been attributed to an acute rejection of renal allograft.

          Methods

          Leukocyte subsets in flow cytometry, complement activation, and concentrations of TGF β, sCD30 (ELISA), and interleukins (CBA) of fifteen patients eligible for renal transplantation were analyzed before, during, and after a regular HD.

          Results

          Before HD, the median proportion of CD8+ effector cells, CD8+ CCR5+ effector cells, and HLA-DR+ regulatory T cells as well as the median concentration of soluble CD30 increased and naive CD8+ T cells decreased. During HD, there was a significant decrease in CD4- CD8- T cells ( p < 0.001) and an increase in CD25+ T cells ( p = 0.026), sCD30 ( p < 0.001), HLA-DR+ regulatory T cells ( p = 0.005), and regulatory T cells ( p = 0.003). TGF β and sCD30 increased significantly over time. The activity of the classical complement pathway started to slightly increase after the first hour of HD and lasted until fifteen minutes after finishing dialysis. The decrease in the functional activity of the alternative pathway was only transient and was followed by a significant increase within 15 minutes after finishing the treatment.

          Conclusion

          HD might interact with the allograft outcome by influencing T cell subsets and activation of the complement system in a biphasic course.

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          Most cited references45

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          Naïve and central memory T-cell lymphopenia in end-stage renal disease.

          End-stage renal disease (ESRD) is associated with increased propensity to infections, diminished response to vaccination, impaired cell-mediated immunity, and reduced CD4+/CD8+ T-lymphocyte ratio. Four subsets of CD4+ and CD8+ T cells have been recently identified: naïve cells (as yet uncommitted), central memory (CM) cells (previously programmed), and CD45RA-positive and CD45RA-negative effector memory (EM) cells (programmed to perform specific effector functions). The effect of ESRD on subpopulations of T lymphocytes is unclear and was studied here. Twenty-one hemodialysis patients and 21 age-matched controls were studied. Pre- and post-dialysis blood samples were obtained and analyzed by three-color flow cytometry. CD4+/CD8+ ratio and the numbers of the naïve and CM CD4+ and CD8+ T cells were significantly reduced, whereas the numbers of EM CD4+ and CD8+ T cells were unchanged in the ESRD group. The reduction of the naïve and CM T-cell counts in the ESRD group was associated with increased apoptosis of these cells. Negative correlations were found between severity of azotemia, oxidative stress, and hyperphosphatemia with the number of naïve T cells. Comparison of diabetic with non-diabetic ESRD patients revealed higher numbers of total CD8+ cells and EM CD8+ T cells in the diabetic group. Dialysis did not significantly change the naïve and CM CD4+ or CD8+ cell counts, but significantly lowered CD8+ EM cell count. Thus, ESRD results in increased apoptosis and diminished populations of naïve and CM T lymphocytes. This phenomenon may, in part, contribute to the impaired immune response in this population.
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            Progressive loss of renal function is associated with activation and depletion of naive T lymphocytes.

            We hypothesized that progressive loss of renal function specifically affects certain T cell subsets. T lymphocyte subsets of patients with chronic kidney disease and healthy controls were characterized by flow cytometry using heparin-anticoagulated whole blood samples. Plasma interleukin (IL)-7 and IL-15 concentrations were determined as these cytokines are critically involved in T cell homeostasis. The results revealed that a progressive decrease in renal function is associated with activation and selective loss of naive T cells and CD4+ central memory cells and a marked increase in CD8+ memory T cells that lack CD45RO and CCR7. The profile of T cell subsets of patients with CKD 5 with or without hemodialysis treatment was similar except for a pronounced shift to Th1 cells in hemodialysis patients. IL-7 but not IL-15 plasma concentrations were lowered in patients with end-stage renal disease as compared to healthy controls.
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              Functional expression of the chemokine receptor CCR5 on virus epitope-specific memory and effector CD8+ T cells.

              Because the chemokine receptor CCR5 is expressed on Th1 CD4(+) cells, it is important to investigate the expression and function of this receptor on other T cells involved in Th1 immune responses, such as Ag-specific CD8(+) T cells, which to date have been only partially characterized. Therefore, we analyzed the expression and function of CCR5 on virus-specific CD8+ T cells identified by HLA class I tetramers. Multicolor flow cytometry analysis demonstrated that CCR5 is expressed on memory (CD28+CD45RA-) and effector (CD28-CD45RA- and CD28-CD45RA+) CD8+ T cells but not on naive (CD28+CD45RA+) CD8+ T cells. CCR5 expression was much lower on two effector CD8+ T cells than on memory CD8+ T cells. Analysis of CCR7 and CCR5 expression on the different types of CD8+ T cells showed that memory CD8+ T cells have three phenotypic subsets, CCR5+CCR7-, CCR5+CCR7+, and CCR5-CCR7+, while naive and effector CD8+ T cells have CCR5-CCR7+ and CCR5+CCR7- phenotypes, respectively. These results suggest the following sequence for differentiation of memory CD8+ T cells: CCR5-CCR7+-->CCR5+CCR7+-->CCR5+CCR7-. CCR5+CD8+ T cells effectively migrated in response to RANTES, suggesting that CCR5 plays a critical role in the migration of Ag-specific effector and differentiated memory CD8+ T cells to inflammatory tissues and secondary lymphoid tissues. This is in contrast to CCR7, which functions as a homing receptor in migration of naive and memory CD8+ T cells to secondary lymphoid tissues.
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                Author and article information

                Contributors
                Journal
                Anal Cell Pathol (Amst)
                Anal Cell Pathol (Amst)
                ACP
                Analytical Cellular Pathology (Amsterdam)
                Hindawi
                2210-7177
                2210-7185
                2019
                25 March 2019
                : 2019
                : 8389765
                Affiliations
                1Institute of Clinical Immunology, Medical Faculty, University of Leipzig, Leipzig, Germany
                2Department of Internal Medicine, Neurology and Dermatology, Clinic for Endocrinology and Nephrology, Section of Nephrology, University Hospital Leipzig, Leipzig, Germany
                3Department of Visceral, Transplantation, Vascular and Thoracic Surgery, University Hospital Leipzig, Leipzig, Germany
                4Institute of Immunology, University of Heidelberg, Heidelberg, Germany
                5Center for Geriatric Medicine, Bezirksklinikum Regensburg, Regensburg, Germany
                6Sigmund Freud PrivatUniversität, Wien, Österreich, Austria
                7Medical Department I, Nephrology Division, University Hospital Ulm, Ulm, Germany
                8Department of Nephrology, KfH Renal Unit, Hospital St. Georg, Leipzig, Germany
                9Martin-Luther-University Halle/Wittenberg, Halle, Germany
                10Institute for Organic Chemistry, University of Leipzig, Leipzig, Germany
                Author notes

                Academic Editor: Alain Chapel

                Author information
                http://orcid.org/0000-0002-7813-0492
                http://orcid.org/0000-0003-4299-8254
                Article
                10.1155/2019/8389765
                6452532
                7cfa72fb-ed7b-445a-9602-e8076ca4015f
                Copyright © 2019 Kristin Mai et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 3 September 2018
                : 4 January 2019
                : 18 February 2019
                Funding
                Funded by: Universität Leipzig
                Funded by: Deutsche Forschungsgemeinschaft
                Categories
                Research Article

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