We also compared the RTL of sorted CD4+CD28null to that of CD4+CD28+ (purity > 95%) T cells and found that the CD4+CD28null T cells had significantly shorter telomeres (P < 0·01) compared to the CD4+CD28+ T cells (Fig. 3d). CMV affected the

CD8+ T cell LDE225 compartment more profoundly than the CD4+ T cell compartment. CMV-seropositive ESRD patients had a significantly (P < 0·05) lower CD8 naive/memory ratio (Fig. 4a), due to a higher number of memory CD8+ T cells consisting of a large population of terminally differentiated CD8+ EMRA T cells (absolute numbers: CMV-seronegative: 0·03 × 106, CMV-seropositive: 0·12 × 106, P < 0·05). This was reflected by the significantly lower CD28+/CD28− PS-341 clinical trial (Fig. 4b) (P < 0·001) and CD57−/CD57+ ratio (Fig. 4c) [P < 0·01 (young) and P < 0·001 (elderly), respectively]. Similarly, as observed for the CD4+ T cell compartment, a significantly higher proportion of CD8+ T cells had a senescent phenotype in CMV-seropositive ESRD patients when compared to their age-matched CMV-seronegative counterparts (young CMV-seropositive: 50·56% ± 3·77 versus young CMV-seronegative: 15·56% ± 4·99, P < 0·01 and old CMV-seropositive: 47·15% ± 4·09 versus old CMV-seronegative: 27·94% ± 5·16, P < 0·05). Also, for the CD8+ T cells we determined the RTL in CD28null and CD28+ T cell-sorted populations. The CD8+CD28null T cells had significantly shorter (P < 0·01) telomeres

than the CD8+CD28+ T cells (Fig. 4d). In an attempt to explain the additional telomere attrition induced by CMV, we determined whether CMV infection induced an increase in the proliferation of CD4+ as well as CD8+ T cells by determining the percentage of Ki-67+ T cells (i.e. the percentage of T cells actually dividing). No significant differences were observed in the percentage of Ki-67+ CD4+ or CD8+ T cells (CD4+Ki-67+ T cells; CMV-seronegative: 2·09% ± 0·68 PRKD3 CMV-seropositive: 1·33% ± 0·52 and CD8+Ki-67+ T cells; CMV-seronegative: 1·99% ± 0·60 CMV-seropositive: 1·34% ± 0·25). The results of this study show

that CMV-seropositivity is associated with more differentiated memory CD4+ and CD8+ T cell compartments. These highly differentiated T cells show loss of CD28 expression, increased expression of CD57 and shorter telomeres. CMV did not affect the thymic output of new naive T cells, and therefore CMV-seropositivity impacts only partly upon the ESRD-related immunological ageing of the T cell system. In a previous study [10], we observed that the characteristics of the peripheral T cell system of ESRD patients are very similar to healthy individuals with a chronological age that is, on average, 20–30 years older. One of the salient findings in ESRD patients and elderly healthy individuals was a decreased number of circulating naive T cells [10]. In humans, the thymus is the single organ involved in naive T cell generation.