Long-term immunological memory against viruses.

This review addresses a novel facet of human T cell biology that constitutes a fundamental problem for long-term maintenance of immunological memory against viruses. The finite proliferative capacity of human T lymphocytes is sufficiently great to accommodate the waves of clonal expansion associated with primary and even secondary immune responses. However, long-term memory to viruses that establish latency and to repeatedly encountered viruses such as influenza may be severely impaired by "replicative senescence", a genetically programmed process affecting most somatic cell types of human origin. Consistent with this idea, memory CD8+ T cells with hallmarks of replicative senescence have been identified in vivo. Such cells may contribute to compromised viral immunity and response to vaccines, and furthermore, their very presence may negatively influence homeostatic mechanisms that control the size of the memory T cell pool in elderly persons.