Expansion of cytolytic CD4+CD28− T cells in end-stage renal disease

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Expansion of cytolytic CD4+CD28− T cells in end-stage renal disease Michiel G.H. Betjes, Martin Huisman, Willem Weimar, Nicolle H.R. Litjens Kidney International Volume 74, Issue 6, Pages 760-767 (September 2008) DOI: 10.1038/ki.2008.301 Copyright © 2008 International Society of Nephrology Terms and Conditions

Figure 1 CD4posCD28null T cells and CMV seropositivity. Percentages of CD4posCD28null T cells of the total number of circulating CD4pos T cells, comparing CMV-seronegative to CMV-seropositive individuals. The CMV-seronegative groups included 30 healthy controls and 30 patients with ESRD. The CMV-seropositive groups included 72 healthy controls and 72 ESRD patients. Kidney International 2008 74, 760-767DOI: (10.1038/ki.2008.301) Copyright © 2008 International Society of Nephrology Terms and Conditions

Figure 2 CD4posCD28null T cells and age. CMV-seropositive ESRD patients (closed symbols, N=70) and age-matched healthy controls (open symbols, N=70) were divided into age groups (≤40, n=9; 41–50, n=17; 51–60, n=18; 60–75, n=26) and either percentages (a) or absolute numbers expressed as 106/l (b) of CD4posCD28null T cells were shown. The Bonferroni-corrected P-value for statistical significance is P<0.006. Kidney International 2008 74, 760-767DOI: (10.1038/ki.2008.301) Copyright © 2008 International Society of Nephrology Terms and Conditions

Figure 3 Age-related increase in CMV-specific IgG titers for ESRD patients but not healthy controls. Mean (±s.e.m.) CMV-specific IgG titers are depicted on the Y axis and expressed as AU/ml, whereas on the X axis, the different age groups are displayed. Open symbols represent the healthy controls and the closed ones, the ESRD patients. A significant (P<0.01, Spearman's rank correlation coefficient) age-dependent increase was noticed for ESRD patients (N=70) but not for healthy controls (N=66). Kidney International 2008 74, 760-767DOI: (10.1038/ki.2008.301) Copyright © 2008 International Society of Nephrology Terms and Conditions

Figure 4 CD28 expression within the different CD4pos T-cell subsets of a CMV-seropositive individual. A representative example of the flow cytometric analysis of CD4pos T cells for a CMV-seropositive individual is shown in (a–c). Panel a shows a typical example of CD28 expression within CD4-positive peripheral blood T cells. The CD28pos (b) and CD28null (c) CD4pos T-cell subsets are further characterized by their expression of CD45RO and CCR7. Using these markers, the following T-cell subsets can be discriminated: naive T cells (Tnaive, CCR7 positive and CD45RO negative), central memory T cells (Tcm, CCR7 positive and CD45RO positive), and effector memory T cells (Tem, CCR7 negative and CD45RO positive). The overall distribution of CD4posCD28null T cells of ESRD patients (n=70) and age-matched healthy controls (n=66) is displayed in (d). The Bonferroni-corrected P-value for statistical significance is P<0.02. Kidney International 2008 74, 760-767DOI: (10.1038/ki.2008.301) Copyright © 2008 International Society of Nephrology Terms and Conditions

Figure 5 Cytotoxic potential of CMV-seropositive individuals. The cytotoxic potential of CD4posCD28null T cells was determined by intracellular staining of unstimulated PBMCs with antibodies directed against granzyme B (a and c) or perforin (b and d). Percentages (a and b) or absolute numbers (c and d) of granzyme B- or perforin-positive CD4posCD28null T are shown. The ESRD patients (n=63) and the age-matched controls (n=63) were divided into a young (<50 years, n=20) and elderly (≥50 years, n=43) group. The Bonferroni-corrected P-value for statistical significance is P<0.007. Kidney International 2008 74, 760-767DOI: (10.1038/ki.2008.301) Copyright © 2008 International Society of Nephrology Terms and Conditions

Figure 6 Percentages and absolute numbers of CD107a- and IFN-γ-expressing CD4posCD28null T cells following CMV-antigen stimulation. Effector functions of CD4posCD28null T cells were determined by stimulating the PBMCs for 6h with CMV-antigen. Percentages and absolute numbers of CD4posCD28null T cells expressing CD107a (a and c) on their cell surface or IFN-γ (b and d) intracellularly were determined using flow cytometry. The ESRD patients (n=62) and the age-matched controls (n=62) were divided into a young (<50 years, n=22) and elderly (≥50 years, n=40) group. The Bonferroni-corrected P-value for statistical significance is P<0.007. Kidney International 2008 74, 760-767DOI: (10.1038/ki.2008.301) Copyright © 2008 International Society of Nephrology Terms and Conditions