Sequential involvement of NK cells and CD8+ T cells in granuloma formation of Rhodococcus aurantiacus-infected mice.
We investigated the effect of in vivo administration of antibodies against T-cell subsets and natural killer (NK) cells on endogenous gamma interferon (IFN-gamma) production and granuloma formation in Rhodococcus aurantiacus-infected mice. High titers of endogenous IFN-gamma were detected in the extracts of the livers and spleens during 24 hr of the infection, reaching the peak at 8 hr, and the IFN-gamma production was reduced by in vivo administration of anti-NK 1.1 monoclonal antibody (MAb) or antibody against asialo GM1+ cells. Endogenous IFN-gamma declined until 2 days of the infection, then reappeared from 1 week and peaked at 3 weeks. Endogenous IFN-gamma at 1 and 3 weeks was reduced by in vivo administration of anti-CD8 MAb, but not by anti-CD4 MAb or anti-NK 1.1 MAb. Granulomatous lesions in the livers and spleens began to appear from 1 week of the infection and developed in 3 weeks. In vivo administration of rat anti-IFN-gamma MAb reduced the development of granulomas. In addition, granuloma formation was reduced by depletion of NK cells prior to the infection or depletion of CD8+ T cells at 1 week of the infection. Based on these findings, it is presumed that the biphasic production of IFN-gamma is attributable to NK cells in the early phase of the infection and CD8+ T cells in the phase of granuloma formation, and that granuloma formation is regulated by NK cells and CD8+ T cells through the secretion of endogenous IFN-gamma.
Asano
M
M
Department of Microbiology, Hokkaido University School of Medicine, Japan.
Nakane
A
A
Kohanawa
M
M
Minagawa
T
T
D000193:Actinomycetales Infections / Q000150:complications*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D015169:Colony Count, Microbial; D005260:Female; D006099:Granuloma / Q000209:etiology* / Q000473:pathology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D007694:Killer Cells, Natural / Q000502:physiology*; D008099:Liver / Q000378:metabolism / Q000382:microbiology; D008107:Liver Diseases / Q000209:etiology* / Q000473:pathology; D008212:Lymphocyte Depletion; D051379:Mice; D008810:Mice, Inbred C57BL; D012240:Rhodococcus; D013154:Spleen / Q000378:metabolism / Q000382:microbiology; D013158:Splenic Diseases / Q000209:etiology* / Q000473:pathology
D000911:Antibodies, Monoclonal; D007371:Interferon-gamma