Modelling T-cell memory by genetic marking of memory T cells in vivo

Immunological memory is the ability of the immune system to respond with en hanced vigour to pathogens that have been encountered in the past. Followin g infection or immunization, most effector T cells undergo apoptotic cell d eath, but a small fraction of these cells, proportional to the early antige n load and initial clonal burst size(1), persist in the host as a stable po ol of memory T cells(2-7). The existence of immunological memory has been r ecognized for over 2,000 years, but our understanding of this phenomenon is limited, primarily because memory lymphocytes cannot be unequivocally iden tified as they lack specific, permanent markers. Here we have developed a t ransgenic mouse model system whereby memory T cells and their precursors ca n be irreversibly marked with a reporter gene and thus can be unambiguously identified. Adoptive transfer of marked CD8(+) T cells specific for lympho cytic choriomeningitis virus protected naive recipients following viral cha llenge, demonstrating that we have marked memory T cells. We also show that cytotoxic effector lymphocytes that develop into memory T cells can be ide ntified in the primary response.