Requirement for neutralizing antibodies to control bone marrow transplantation-associated persistent viral infection and to reduce immunopathology.
Bone marrow transplantation (BMT) is commonly used in the treatment of leukemia, however its therapeutic application is partly limited by the high incidence of associated opportunistic infections. We modeled this clinical situation by infecting mice that underwent BMT with lymphocytic choriomeningitis virus (LCMV) and investigated the potential of immunotherapeutic strategies to counter such infections. All mice that received BMT survived LCMV infection and developed a virus carrier status. Immunotherapy by adoptive transfer of naive splenocytes protected against low (200 PFU), but not high (2 x 10(6) PFU), doses of LCMV. Attempts to control infection of high viral titers using strongly elevated frequencies of activated LCMV-specific T cells failed to control virus and resulted in immunopathology and death. In contrast, virus neutralizing Abs combined with naive splenocytes were able to efficiently control high-dose LCMV infection without associated side effects. Thus, cell transfer combined with neutralizing Abs represented the most effective means of controlling BMT-associated opportunistic viral infection in our in vivo model. These data underscore the in vivo efficacy and immunopathological "safety" of neutralizing antibodies.
Lang
Karl S
KS
Institute of Experimental Immunology, University Hospital, Zurich, Switzerland. karl.lang@usz.ch
Recher
Mike
M
Navarini
Alexander A
AA
Freigang
Stefan
S
Harris
Nicola L
NL
van den Broek
Maries
M
Odermatt
Bernhard
B
Hengartner
Hans
H
Zinkernagel
Rolf M
RM
D019264:Adoptive Transfer; D000818:Animals; D000906:Antibodies / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation / Q000276:immunology* / Q000473:pathology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D007116:Immunization, Passive; D008216:Lymphocytic Choriomeningitis / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009894:Opportunistic Infections / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D014766:Viremia / Q000276:immunology / Q000473:pathology / Q000628:therapy; D014779:Virus Replication / Q000276:immunology*
D000906:Antibodies