Increased Resistance to Cytomegalovirus in Graft-versus-Host Immunosuppressed F1 Mice by Pre-Immunization

Abstract

Graft-versus-host (GvH) immunosuppression was induced in (C57BL/10xB10.A)F1 hybrid mice by intravenous inoculation of 30x10⁶ parental (B10.A) spleen cells. This treatment caused the normally resistant F1 mice to become highly susceptible to cytomegalovirus (CMV) challenge delivered 7 or 14 days later (survival below 10%). This susceptibility was reversed by immunization with live CMV by either intraperitoneal (i.p.) or subcutaneous route prior to GvH immunosuppression and challenge (survival greater than 87%). Mice which were immunized by the i.p. route and subsequently immunosuppressed without then being challenged had significantly higher mortality due to recrudescent CMV infection than similarly treated mice that did receive a challenge. These data suggested a boosting effect of the challenge in immunized mice. In vitro cell mediated responses to trinitrophenyl (TNP) modified self and allogeneic histocompatibility antigens were abrogated in all GvH groups 10 days after parental cell inoculation which demonstrated that GvH immunosuppression was reversed only for CMV. The CMV specific humoral antibody (Ab) response was monitored using an enzyme linked immunosorbent assay (ELISA) method. The CMV was highly immunogenic in pre-GvH F1 mice as demonstrated by a rapid rise in IgG Ab titer. In GvH immunosuppressed mice, the titer peaked after parental cell administration and then declined rapidly. The titers were high at the time of challenge and specific Ab may have contributed to defense against challenge. The effect of the post GvH challenge in preventing recrudescent CMV infection could not be explained in terms of protecting Ab since titers declined in both cases.