Prevalence of circulating CD4+CD28null T cells is associated with early atherosclerotic damage in patients with end-stage renal disease undergoing hemodialysis.
CD4(+) T-cell subsets lacking surface CD28 in peripheral blood have been suggested to predispose people to atherosclerosis. To determine if CD4(+)CD28(null) T cells are involved in the immunopathological process of atherosclerotic damage in end-stage renal disease (ESRD) patients undergoing hemodialysis (HD), we characterized peripheral-blood CD4(+)CD28(null) T cells from HD patients and investigated the association between these cells and early atherosclerotic damage. Four color flow cytometric analyses showed that HD patients had significantly higher percentages of CD4(+)CD28(null) T cells in circulating blood than healthy subjects (HS). Most HD patient-derived CD4(+)CD28(null) T cells expressed higher levels of CX3CR1 and produced more intracellular IFN-γ, perforin and granzyme B than their counterparts. Regression analyses demonstrated that the increased levels of CD4(+)CD28(null) T cells were positively correlated to serum levels of C-reactive protein, suggesting systemic inflammation and atherosclerosis. Furthermore, phenotypic and functional studies of CD4(+)CD28(null) T cells showed that these cells were closely correlated with impaired flow-mediated vasodilation and increased intima-media thickness in the carotid artery, which are markers of early atherosclerosis. These data suggested that CD4(+)CD28(null) T cells are important effector cells in HD patients, and that these cells may have a critical role in mediating early atherosclerotic damage.
Nanjing Medical University, Affiliated Second Hospital, Department of Nephrology, China. sunzhip@126.com
Zhiping
Z
Sun
Hong
H
Ye
Bing
B
Tang
Xia
X
Shen
Xiaochun
X
Wu
Hua
H
Zhong
Weizong
W
Song
D000328:Adult; D000368:Aged; D050197:Atherosclerosis / Q000097:blood / Q000150:complications / Q000276:immunology / Q000473:pathology*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis / Q000276:immunology; D018106:CD28 Antigens / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D000073883:CX3C Chemokine Receptor 1; D017536:Carotid Artery, Common / Q000276:immunology / Q000473:pathology; D059168:Carotid Intima-Media Thickness; D016022:Case-Control Studies; D005260:Female; D005434:Flow Cytometry; D053804:Granzymes / Q000097:blood / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000097:blood / Q000276:immunology; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications / Q000276:immunology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D054353:Perforin / Q000097:blood / Q000276:immunology; D019707:Receptors, Chemokine / Q000097:blood / Q000276:immunology; D006435:Renal Dialysis; D013997:Time Factors
D015415:Biomarkers; D018106:CD28 Antigens; D000073883:CX3C Chemokine Receptor 1; C095235:CX3CR1 protein, human; D019707:Receptors, Chemokine; D054353:Perforin; D007371:Interferon-gamma; D002097:C-Reactive Protein; D053804:Granzymes