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Intravenous administration of 6-O-mycoloyl-N-acetylmuramyl-L-alanyl-D-isoglutamine (mycol-MDP) together with a specific antigen, PPD, in a water-in-oil emulsion was found to produce lung granuloma and to provide a low but significant grade of protection in mice against tuberculous infection within 4 weeks. However, these products, when given in an oil-in-water emulsion did not produce granuloma. Mycol-MDP alone produced comparable lung granuloma in both C57Bl/6 mice, high responders to BCG cell walls (CW), and C3H/He mice, low responders, 1 week after the injection, and when challenged at this time by aerosol containing virulent bovine tubercle bacilli, they showed significantly increased resistance. The present results confirmed the close relationship between lung granuloma and protection against aerosol challenge with Ravenel and revealed that the extent of lung granuloma at the time of aerosol challenge is crucial for the development of protection in mice immunized with mycol-MDP plus PPD as it is in mice immunized with BCG CW. However, these findings are not always the case for lung granuloma induced with mycol-MDP alone.
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