ON THE ROLE OF ANTIGEN IN MAINTAINING CYTOTOXIC T-CELL MEMORY

This study evaluated whether T-cell memory reflects increased precurso r frequencies of specific long-lived T cells and/or a low-level immune response against some form of persistent antigen. Antivirally protect ive CD8(+) T-cell memory was analyzed mostly in the original vaccinate d host to assess the role of antigen in its maintenance. T-cell mediat ed resistance against reinfection was measured in the spleen and in pe ripheral solid organs with protocols that excluded protection by antib odies. In vivo protection was compared with detectable cytotoxic T-lym phocyte precursor frequencies determined in vitro. In the spleen, in v itro detectable cytotoxic T-lymphocyte precursor frequencies remained stable independently of antigen, conferring resistance against viral r eplication in the spleen during reinfection. In contrast, T-cell media ted resistance against reinfection of peripheral solid organs faded aw ay in an antigen-dependent fashion within a few days or weeks. We show that only memory T cells persistently or freshly activated with antig en efficiently extravasate into peripheral organs, where cytotoxic T l ymphocytes must be able to exert effector function immediately; both t he capacity to extravasate and to rapidly exert effector function crit ically depend on restimulation bg antigen. Our experiments document th at the duration of T-cell memory protective against peripheral reinfec tion depended on the antigen dose used for immunization, was prolonged when additional antigen was provided, and was abrogated after removal of antigen. We conclude that T-cell mediated protective immunity agai nst the usual peripheral routes of reinfection is antigen-dependent.