A FUNCTIONAL AND KINETIC COMPARISON OF ANTIVIRAL EFFECTOR AND MEMORY CYTOTOXIC T-LYMPHOCYTE POPULATIONS IN-VIVO AND IN-VITRO

To analyze the critical parameters for effective antiviral cytotoxic T lymphocyte (CTL) activity in vivo, control of lymphocytic choriomenin gitis virus (LCMV) infection in the spleen was studied after adoptive transfer of different spleen cell populations into preinfected recipie nts. The quantitative, qualitative and kinetic requirements for virus control were defined and related to in vitro assays to compare the ant iviral protective function of CTL from naive, acutely infected and mem ory mice. Treatment of mice with an established but limited LCMV infec tion by adoptive transfer of spleen cells from acutely LCMV-infected m ice led to complete virus elimination mainly mediated by donor-derived CD8(+) T cell-mediated, perforin-dependent cytotoxicity. Since virus is continuously spreading and the number of infected target cells rapi dly increases, the time until target cell lysis is achieved was critic al: if release of viral progeny was not prevented early, additional ti me to perform effector function did not improve overall virus control. When the function of various cell populations was compared in this mo del, we found that CTL from naive and memory mice perform considerably less well than CTL from acutely infected mice. In vitro studies indic ated that this is probably due to the fact that they can not fulfill t he limiting time requirements for immediate antiviral protection: whil e CTL from acutely infected mice can perform lyric effector function i mmediately, memory CTL require a considerable reactivation time before they can lyse infected target cells. This reactivation does not neces sarily involve cell division. These findings illustrate how critical t ime limitations are for CTL to mediate early control of a dynamic viru s infection in vivo.