Impaired virus control and severe CD8+ T-cell-mediated immunopathology in chimeric mice deficient in gamma interferon receptor expression on both parenchymal and hematopoietic cells.
Bone marrow chimeras were used to determine the cellular target(s) for the antiviral activity of gamma interferon (IFN-gamma). By transfusing such mice with high numbers of naive virus-specific CD8(+) T cells, a system was created in which the majority of virus-specific CD8(+) T cells would be capable of responding to IFN-gamma, but expression of the relevant receptor on non-T cells could be experimentally controlled. Only when the IFN-gamma receptor is absent on both radioresistant parenchymal and bone marrow-derived cells will chimeric mice challenged with a highly invasive, noncytolytic virus completely lack the ability to control the infection and develop severe wasting disease. Further, the study shows that IFN-gamma receptor expression on parenchymal cells in the viscera is more important for virus control than IFN-gamma receptor expression on bone marrow-derived cells.
Henrichsen
Pernille
P
Institute of Medical Microbiology and Immunology, University of Copenhagen, Denmark.
Bartholdy
Christina
C
Christensen
Jan Pravsgaard
JP
Thomsen
Allan Randrup
AR
D000818:Animals; D001117:Arenaviridae Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D001854:Bone Marrow Cells / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002678:Chimera; D008099:Liver / Q000276:immunology / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017471:Receptors, Interferon / Q000172:deficiency / Q000235:genetics; D013154:Spleen / Q000276:immunology / Q000821:virology; D019282:Wasting Syndrome / Q000473:pathology; D000096743:Interferon gamma Receptor
D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor