Influence of end stage renal disease on CD28 expression and T‐cell immunity

Abstract

Background T‐cell immunity is affected in end stage renal disease (ESRD). However, whether this happens at pre‐ or post‐dialysis stage and what is the impact of different renal replacement methods, remains unclear. We investigated the alterations of T‐cell subtypes in patients at pre‐dialysis ESRD and their further changes during dialysis. Methods CD4+, CD8+, CD4 + CD28null and CD8 + CD28null T‐cells were analysed in 40 ESRD patients at two different time points, (a) the day started on dialysis (ESRD‐T0) and (b) 6 months later (ESRD‐T6), while being on haemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD). Twenty‐five age matched healthy volunteers served as controls. Results CD4+ and CD8+ T‐cells were significantly reduced in ESRD‐T0 patients compared to controls, 604 (105‐3551) vs 943 (584‐1867)μ/L, P = .001, and 352 (103‐1561) vs 422.4 (263‐1453)μ/L, P = .05, respectively. However, proportions of CD4 + CD28null and CD8 + CD28null cells were significantly increased, 6.4 (0.3‐30)% vs 2.7 (0.1‐7.8)%, P = .04 and 58.2 (12.8‐85.4)% vs 39 (7.8‐57.1)%, P = .01, respectively. Proportion of CD4 + CD28null cells showed significant correlation with serum CRP (r = .4, P = .04) and albumin levels (r = −.5, P = .007) in ERSD patients. ESRD‐T0 patients with cardiovascular disease (CVD) had increased CD4 + CD28null and CD8 + CD28null proportions, 8.6 (1‐30)% vs 2.1 (0.1‐19.8)%, P = .04 and 62.5 (12.8‐85.4)% vs 45.5 (5.7‐73.7)%, P = .02, respectively, compared to those without. Six months later, both CD4 + CD28null and CD8 + CD28null T‐cells were increased in HD compared to CAPD patients, by +110.11 (−27.1 to 311.4)% vs −28.1 (−100 to 30)%, P = .003 and +55.23 (−29.06 to 197.93)% vs −8.34 (−54.99 to 66.72)%, P = .05, respectively. Conclusions CD4 + CD28null and CD8 + CD28null T‐cells are increased at pre‐dialysis ESRD, and correlate with chronic inflammatory markers and the presence of CVD. Dialysis methods seem to have different impact on these subpopulations.

CD28null and Regulatory T Cells Are Substantially Disrupted in Patients with End-Stage Renal Disease Due to Diabetes Mellitus

“…Only recently were CD8+CD28null cells found to accumulate in atherosclerotic plaques and act as independent predictors of cardiovascular events in ESRD. Regardless of the presence of DM, HD and CAPD have opposing effects in the existence and accumulation of CD28null cells, with CAPD causing a significant amelioration in CD28null cells [10]. In the present study, patients with ESRD due to diabetic nephropathy had a further significant increase in these cells, while nondiabetics were not severely affected by HD.…”

“…The different ways in which dialysis methods affect T lymphocyte subpopulations and their strong impact on mainly diabetic patients is a completely novel finding. Although the effect of ESRD on the expression of the CD28 molecule was proven, and many investigators agree that patients on chronic kidney disease stages IV-V show a significant increase in the frequency of CD4+CD28null cells, the further effect of dialysis is controversial, with some investigators finding no differences between predialysis and dialysis-dependent ESRD patients, and others showing CD28null cells further expanding in patients on HD [10,35,36]. However, all previous studies focused only on CD4+CD28null cells, excluding CD8+CD28null cells as clinically unimportant.…”

“…In all patients, the immunological risk profile (IRP) was estimated as was described before on the basis of the levels of CD4+ and CD8+ cells, the CD4/CD8 ratio, and the percentage of CD28null cells [10].…”

“…Immune disorders and clinical consequences gradually progress during the deterioration of renal function towards reaching ESRD, and they are characterized by an increased risk of cardiovascular disease, infections, and malignancies, leading to increased morbidity and mortality [8][9][10]. Changes in white-cell count and their subtypes are evident, but alterations in T-cell subpopulations seem to play a prominent role in the development of long-term clinical complications [11,12].…”

“…CD28 in the only costimulatory receptor constitutively expressed on naive T cells; therefore, its presence is fundamental for the initiation and maintenance of T-cell-mediated immune responses [16,17]. In chronic-inflammation situations such as chronic kidney disease and diabetes mellitus (DM), the transformation of receptor repertoire on T cells, including the loss of the CD28 molecule, results in a cell type of which the phenotype and activities resemble NK cells, called the NK-like T cell [2,10,11,18,19].…”