SEQUENTIAL INVOLVEMENT OF NK CELLS AND CD8(-CELLS IN GRANULOMA-FORMATION OF RHODOCOCCUS AURANTIACUS-INFECTED MICE() T)

We investigated the effect of in vivo administration of antibodies aga inst T-cell subsets and natural killer (NK) cells on endogenous gamma interferon (IFN-gamma) production and granuloma formation in Rhodococc us aurantiacus-infected mice. High titers of endogenous IFN-gamma were detected in the extracts of the livers and spleens during 24 hr of th e infection, reaching the peak at 8 hr, and the IFN-gamma, production was reduced by in vivo administration of anti-NK 1.1 monoclonal antibo dy (MAb) or antibody against asialo GM1(+) cells. Endogenous IFN-gamma declined until 2 days of the infection, then reappeared from 1 week a nd peaked at 3 weeks. Endogenous IFN-gamma at 1 and 3 weeks was reduce d by in vivo administration of anti-CDS MAb, but not by anti-CD4 MAb o r anti-NK 1.1 MAb. Granulomatous lesions in the livers and spleens beg an 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. Tn addition, granuloma formation was reduced by deplet ion 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 th at 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 g ranuloma formation, and that granuloma formation is regulated by NK ce lls and CD8(+) T cells through the secretion of endogenous IFN-gamma.