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.