Differential effects of age, cytomegalovirus-seropositivity and end-stage renal disease (ESRD) on circulating T lymphocyte subsets

End-stage renal disease (ESRD) is associated with an immune defect characterized by increased susceptibility for infections and decreased humoral responses to T-cell dependent antigens like HBsAg [1,2]. Circulating T lymphocytes can be dissected into subsets of na？ve and memory T lymphocytes using the common leukocyte antigen CD45RO (memory marker) and the chemokine receptor CCR7 which is important for homing of T cells to lymphoid organs. Differential expression of CD45RO and CCR7 allows for further dissection of functionally different T lymphocyte subsets; na？ve T cells (Tnaive, expressing CCR7), central-memory T cells (Tcm, expressing CCR7) and effector-memory (Tem, no expression of CCR7) [3]. In addition, within the CD8+ T lymphocyte subset an extra late effector memory population can be distinguished, lacking both CCR7 and CD45RO (Temra) [4,5]. The loss of expression of the co-stimulatory molecule CD28 and increased expression of CD57 on memory T cells is indicative of a later stage of differentiation of T cells with diminished replicative capacity [6].Progressive loss of renal function is associated with a progressive decrease in the size of the the na？ve T cell compartment, a decrease within CD4+ Tcm lymphocytes and a significant increase in CD8+ Temra [7,8]. In addition, we have demonstrated that the severely impaired humoral response of ESRD patients to HBV vaccination can be attributed to a specific deficit in the generation of antigen-specific effector-memory CD4+ T cells [9]. Therefore, the disturbed composition of circulating T cells in ESRD patients seems to underly, at least partly, their immune deficiency.Cytomegalovirus (CMV) seropositivity is known to have a major impact on the repertoire of antigen specific T cells as an estimated 10% of circulating T cells is CMV-antigen specific in seropositive individuals [10]. In addition, the changes generally observed with an aged immune system, like a decreased CD4/CD8 ratio and expansion of CD28 negative C