Too much memory?

Abstract

The decline of the adaptive immune response in elderly individuals is thought to be a major contributor to the increased morbidity and mortality associated with infectious diseases in this group. One potential reason for this decline is an increase in oligoclonal T cells with a memory phenotype, and a concomitant decrease in naive T cells owing to declining thymus function.Khan et al. [1xCytomegalovirus seropositivity drives the CD8 T cell repertoire towards greater clonality in healthy elderly individuals. Kahn, N. et al. J. Immunol. 2002; 169: 1984–1992PubMedSee all References][1] have investigated the relationship between cytomegalovirus (CMV) infection and oligoclonal expansion of the CMV-specific cytotoxic T lymphocyte (CTL) population in volunteers aged 60–90 years old. Their results indicate that elderly individuals have a significantly larger CMV-specific memory T cell population with highly restricted clonality. This population could constitute up to 23% of total CD8 T cells in some individuals. In addition, larger expansions correlated with greater clonal restriction – sometimes down to a single T cell clone. When comparing global CD8 clonality (not just in CMV-specific cells) by RT-PCR of T-cell receptor sequences, the authors found significantly more clonal expansions in CMV-positive individuals than in CMV-negative individuals.These results indicate that the oligoclonal expansions seen in old age are probably associated with chronic sub-clinical infections such as CMV infections. This suggests that over time, sub-clinical infection tightly focuses a significant portion of the immune system on a single pathogen or even a single peptide epitope. Although there is no evidence for a direct link between a decrease in T-cell repertoire and declining immune function, it is possible that a smaller T-cell repertoire will impair the immune response to new or recurrent pathogens.