Abstract
The age- and cytomegalovirus (CMV)-seropositivity-related changes in subsets and differentiation of circulating T cells were investigated in end-stage renal disease (ESRD) patients (n = 139) and age-matched healthy individuals. The results show that CMV-seropositivity is associated with expansion of both CD4+ and CD8+ memory T cells which is already observed in young healthy individuals. In addition, CMV-seropositive healthy individuals have a more differentiated memory T cell profile. Only CMV-seropositive healthy individuals showed an age-dependent decrease in CD4+ naïve T cells. The age-related decrease in the number of CD8+ naïve T cells was CMV-independent. In contrast, all ESRD patients showed a profound naïve T-cell lymphopenia at every decade. CMV-seropositivity aggravated the contraction of CD4+ naïve T cells and increased the number of differentiated CD4+ and CD8+ memory T cells. In conclusion, CMV-seropositivity markedly alters the homeostasis of circulating T cells in healthy individuals and aggravates the T cell dysregulation observed in ESRD patients.
Highlights
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 naïve and memory T lymphocytes using the common leukocyte antigen CD45RO 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; naïve T cells (Tnaive, expressing CCR7), central-memory T cells (Tcm, expressing CCR7) and effector-memory (Tem, no expression of CCR7) [3]
Summary
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 naïve 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. Progressive loss of renal function is associated with a progressive decrease in the size of the the naïve T cell compartment, a decrease within CD4+ Tcm lymphocytes and a significant increase in CD8+ Temra [7,8]. 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]. The disturbed composition of circulating T cells in ESRD patients seems to underly, at least partly, their immune deficiency
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