Dysfunctional CMV-specific CD8+ T cells accumulate in the elderly

Large clonal expansions of peripheral CD8(+) T cells carrying receptors for single epitopes of CMV are common in the elderly and may be associated with an immune risk phenotype predicting mortality. To study the effect of ageing on the ability of CMV-specific CD8(+) T cells to produce type 1- and type 2-cytokines, interferon-gamma-and IL-10-producing, CD8(+) T cell responses in the presence of CMV peptide antigen were measured in CMV-seropositive old and young donors. We found that large expansions of A2/NLV-specific CD8(+) T lymphocytes in the elderly are accompanied by a partial loss of antigen responsiveness as reflected in a greatly decreased frequency of antigen-specific IFN-gamma-and IL-10-producing cells. Thus, despite carrying specific antigen receptors, the majority of the clonally expanded CMV-specific CD8(+) cells in the elderly was dysfunctional according to these criteria. Our data indicated a bias towards a more anti-inflammatory response in the elderly. The accumulation of dysfunctional CMV-specific cells might fill the 'immunological space' and decrease the available repertoire of T cells for novel antigens. This might account for the increased incidence of many infectious diseases in the elderly.