T-cell aging in end-stage renal disease: an evolving story with CMV

Established evidence from the last decade has suggested that chronic cytomegalovirus infection has strong impact on the human immune system, resulting in aggravated aging-associated T-cell changes that are associated with poorer vaccination responses, cardiovascular disease and shortened survival. Patients with end-stage renal disease (ESRD), the most severe form of chronic kidney disease, exhibit premature aging phenotypes in almost all organ systems, including the immune system. Longitudinal studies of T-cell aging in healthy humans have been scanty because it requires a large number of study subjects and a study duration for decades. In recent years, it became clear that ESRD patients with cytomegalovirus (CMV) infection exhibit enhanced aging-related immune changes than CMV-seropositive individuals without renal disease, including chronic inflammation, decreased numbers of naïve CD4+ and CD8+ T cells, increased clonality of memory T cells with skewed repertoire and shortened telomeres. These findings lead to the hypothesis that the uremic milieu and treatment for renal failure can lead to premature aging of T cells independent from CMV infection and suggest that ESRD can be an important disease model for studying human aging. Future studies deciphering the underlying mechanisms of accelerated T cell aging in ESRD patients may eventually reveal additional insights into T-cell persistence and function during aging in CMV-seropositive, non-ESRD individuals.