Recovery from experimental rabies by adoptive transfer of immune cells.

Abstract

The transient, sublethal infection produced by intracerebral inoculation of the Flury high egg passage (HEP) strain of rabies virus into adult mice was converted into a lethal one (approx. 80 to 100% mortality) by administering 150 mg/kg cyclophosphamide (CY) 2 days after infection. Immunosuppressed, infected animals showed no immunological response to rabies and died 15 to 20 days after infection. However, mortality was reduced to 12% when suppressed mice were adoptively immunized, 4 days after infection, with an intravenous injection of 60 X 10(6) spleen cells from rabies-immune syngeneic donors. The lymphocytes obtained early after donor immunization (4 to 11 days) reduced mortality, whereas those obtained late (16 to 32 days after immunization) were not effective. The ability of donor cells to protect animals corresponded very closely with donor cytotoxic T lymphocyte (CTL) activity. Within 4 days after immune cell transfer, serum neutralizing antibody and CTL levels in recipients were comparable to those found in virus-infected control animals. Immune donor cells were fractionated into thymus-derived (T-enriched) and bone marrow-derived (B-enriched) subsets. The T and B subsets reduced mortality to 32% and 34% respectively. CTL and serum neutralizing antibody responses could be detected in these animals, although they appeared later than in mice treated with unfractionated immune spleen cells. The present study demonstrates that both B and T lymphocytes are required for optimum clearance of rabies from the central nervous system (CNS) and suggests a functional role for rabies-specific CTL in vivo.