CD4+ CD28null cells are expanded and exhibit a cytolytic profile in end-stage renal disease patients on peritoneal dialysis

Background. End-stage renal failure patients, including those on peritoneal dialysis (PD), exhibit several nontraditional cardiovascular (CV) risk factors. A role of CD4(+)CD28(null) T lymphocytes in the genesis of coronary artery disease (CAD) has been proposed. We investigated this cell population and examined its phenotype in a cohort of PD patients without CV disease. Methods. The frequency of the peripheral blood CD4+ CD28null T-cell compartment and cytotoxic characteristic of these cells (as assessed by perforin and granzyme B expressions) were determined in 33 PD patients without CAD and 20 healthy subjects by two-and three-color flow-cytometry. High-sensitivity C-reactive protein (hs-CRP) was determined by enzyme-linked immunosorbent assay. We investigated whether there was a correlation between these cells and traditional CV risk factors. Results. Compared to healthy controls, CD4(+)CD28(null) T cells were significantly expanded in PD patients (10.30 +/- 2.03% versus 3.55 +/- 0.67%, mean +/- SE, P = 0.0007). Perforin and granzyme B expressions were restricted to CD4(+)CD28(null) T cells compared to CD4(+)CD28(+) T cells (< 0.0001). A greater proportion of CD4(+)CD28(null) T cells in PD patients expressed these molecules (P = 0.007 and 0.04). hs-CRP level was increased in PD patients (P < 0.0001) but did not correlate with the CD4(+)CD28(null) T-cell frequency. Increasing age correlated with the CD4(+)CD28(null) cells. Conclusions. PD patients exhibit a substantially increased number of circulating CD4(+)CD28(null) T cells that show a cytolytic profile before the onset of clinically significant CAD. Their significance as a nontraditional CV risk factor needs further studies.