Consequences of Cyclophosphamide Treatment in Murine Lymphocytic Choriomeningitis: Evidence for Cytotoxic T Cell Replication in Vivo

Abstract

Administration of a large dose (400 mg/kg) of cyclophosphamide (Cy) prior to infection with lymphocytic choriomeningitis virus (LCMV) suppresses the virus-immune cytotoxic T lymphocyte (CTL) response. Treatment with 150 mg/kg of Cy before, at the time of, or on the day after LCMV infection has little effect on CTL function. In contrast, when given on 2-7 days after LCMV, this dose profoundly depresses the day-8 CTL response and delays the onset of neurological disease. Administration of as little as 50 mg/kg of Cy has a marked effect on CTL activity when given 5 days after virus. Therefore it seems likely that CTL are replicating for 5 or 6 days during this primary response. Mulitplication of these T cells is apparently completed by day 8, since inoculation of 150 mg/kg of Cy at this time has little effect on the level of CTL activity measured on day 9. The CTL activity is not reconstituted by in vitro culture with added helper factors. The interpretation that CTL are replicating in vivo following inoculation of LCMV is in accord with other analyses of virus-specific precursor frequency in primed and naive mice.