Further study on relationship of anti-tuberculous protection to lung granulomata produced by intravenous injections of synthetic 6-0-mycoloyl-N-acetyl-muramyl-L-alanyl-D-isoglutamine with or without specific antigens.

The synthetic adjuvant, 6-0-mycoloyl-n-acetylmuramyl-L-alanyl-D-isoglutamine (mycol-MDP), is know to have a similar activity to the adjuvant moiety which resides in BCG cell walls (CW). Mycol-MDP plus a specific antigen, PPD, produced lung granulomata followed by anti-tuberculous protection in BCG CW high responder C57BL/6 (B6) mice, but not in low responder C3H/HeMs) (C3H) mice when a granuloma assay and an aerosol challenge with Mycobacterium bovis, Ravenel were carried out 4 weeks after the injection. However, when the granuloma assay and mycobacterial infection were performed 1 week after the injection, both B6 and C3H mice showed slight but definite lung granuloma formation accompanied by detectable protection. This suggested that the early development of granuloma was elicited by direct activation of macrophages with mycol-MDP. This possibility was confirmed since T-cell-deprived (B) mice produced lung granulomata 1 week after injection with mycol-MDP alone. However, contrary to our expectation, these B mice did not show anti-tuberculous protection. The role of T cells for anti-tuberculous immunity is discussed in relation to the adjuvant activity of mycol-MDP.