Large numbers of dysfunctional CD8+ T lymphocytes bearing receptors for a single dominant CMV epitope in the very old

Longitudinal studies suggest that a set of immune parameters including high percentages of peripheral CD8(+), CD28(-), CD57(+) T lymphocytes, low CD4 and B cell counts, and poor T cell proliferative responses to mitogens is associated with decreased remaining longevity in the free-living very elderly (> 85 years). This combination of immune parameters was also significantly associated with an inverted CD4/CD8 ratio and cytomegalovirus seropositivity. Here, using tetramer technology, we show markedly increased numbers of CD8(+) T cells bearing receptors for one single CMV epitope in the very elderly. Moreover, the fraction of these tetramer-reactive cells secreting interferon-gamma after specific antigenic stimulation was significantly lower in the old than in the young, as was the percentage of CD28- positive cells in this population. Therefore, we conclude that marked expansions of CMV-specific CD8(+) T cells have occurred and that the obsession of a large fraction of the entire CD8(+) T cell subset with one single viral epitope may contribute to the increased incidence of infectious disease in the elderly by shrinking the T cell repertoire available for responses to other antigens.