CYTOLYTICALLY ACTIVE MEMORY CTL PRESENT IN LYMPHOCYTIC CHORIOMENINGITIS VIRUS-IMMUNE MICE AFTER CLEARANCE OF VIRUS-INFECTION

Generally, it has been assumed that memory T cells are dormant and ina ctive cells in the absence of their specific Ag. Recent work has chall enged this assumption by showing that a portion of the CD8(+) memory T cell pool is in cycle. In this study, we demonstrate that a significa nt number of blast-size memory CD8(+) T cells in mice, long after lymp hocytic choriomeningitis virus (LCMV) infection, mediate cytolysis aga inst highly sensitive targets without any in vivo or in vitro restimul ation and expansion with Ag. Peptide-coated RMA-S targets were suffici ently sensitive to detect low but significant cytolytic activity in bu lk Cr-51 release assays in nonstimulated LCMV-specific splenic memory CTL populations. Most of the directly cytotoxic activity was against t he GP33 epitope, and this persisted throughout the lifetime of the mou se following infection. The cytotoxic activity was not inhibited by cy closporin A, indicating that these cells were already in an active sta te and not dependent on further stimulation in vitro. It was formally shown that the cytotoxic activity was mediated by the CD8(+) CTL by so rting for the blast-size CD8(+) population and by blocking target cell lysis with anti-CD8 Ab. Thus, at any time after the original infectio n some portion of the memory CD8(+) T cell pool is cycling, and it rem ains cytolytically active long after resolution of the original infect ion. These CTL may provide a rapidly acting defense mechanism against reinfection.