PROTECTION AGAINST IMMUNOPATHOLOGICAL CONSEQUENCES OF A VIRAL-INFECTION BY ACTIVATED BUT NOT RESTING CYTOTOXIC T-CELLS - T-CELL MEMORY WITHOUT MEMORY T-CELLS

Immunological memory is a key characteristic of specific immune respon ses. Persistence of increased levels of precursor T cells is antigen-i ndependent and is often used as an indicator of T cell memory. This st udy documents that, depending on the chosen readout, cytotoxic T lymph ocyte (CTL) memory against lymphocytic choriomeningitis virus (LCMV) a ppears long- or short-lived in the absence of persisting antigen. To s tudy T cell memory in the absence of persisting antigen, either short- lived antigens were used for immunization or adoptive transfer methods were used to eliminate possibly persisting antigen. These experiments revealed that increased specific precursor frequencies and CTL-mediat ed protection against an i.v. infection with LCMV were long lived. In contrast, CTL-mediated protection against a peripheral infection of th e skin with LCMV, or of the ovary with recombinant vaccinia virus, was short-lived. These results show that maintenance of increased specifi c CTL precursor frequencies and central T cell memory in lymphoid tiss ue (where preexisting neutralizing antibodies usually provide protecti on anyway) is long-lived and antigen-independent. In contrast, in prot ection against peripheral viral infections, where the relative kinetic s of virus growth and virus elimination by T cells are of key importan ce, T cell memory is short-lived in the absence of antigen, This indic ates that peripheral T cell memory in antibody-inaccessible tissues is mediated by antigen-activated effector T cells and apparently not by specialized memory T cells.