In vitro evidence of cell-mediated immunity after exposure of mice to both live and inactivated rabies virus.

Mice exposed to live or beta-propiolactone-inactivated rabies virus generated a strong, specific cell-mediated cytotoxic response which was generally maximal 6 days after inoculation. Release of 51Cr was apparently a function of immune thymus-derived lymphocytes (T cells) because it was abrogated by prior incubation of spleen cells with anti-thymus antiserum and complement but was undiminished by passage of spleen cells through nylon-wool columns. Cytotoxicity was always maximal for interactions in which thymus-derived cells and targets shared H-2 genes but, unlike the situation found in other assays of this type, considerable lysis of allogeneic, virus-infected target cells may also occur. Perhaps the most significant finding from these experiments is that an inactivated virus has been shown to stimulate a potent cytotoxic thymus-derived cell response. Manipulation of this experimental model may allow analysis of the antigens required for stimulation of cell-mediated immunity. A more practical consequence may be the development of more rational protocols for postexposure vaccination against rabies. Prior treatment of mice with antirabies antibody severely depressed the generation of cell-mediated immunity.