Propionibacterium, Corynebacterium, Mycobacterium and Lepra bacilli.

Evidence is presented which suggests that certain key markers of lepra bacilli reside collectively in Proprionibacterium acnes, Corynebacterium tuberculostearicum and Mycobacterium leprae. The unrestricted replication of Mycobacterium leprae depends most probably upon the presence of an immune-deficiency-inducing viral agent or possibly on the combined effects of the organisms considered.

Immunosuppressive activities of peritoneal and splenic macrophages in murine leprosy: effect on lymphocyte transformation and tumor growth.

The ability of peritoneal macrophages (PM) and splenic macrophages (SM) to suppress tumor growth and lymphocyte transformation in vitro was studied in infected mice with Mycobacterium lepraemurium (MLM). Both PM and SM of leprous mice showed cytostatic activity against tumor cells in vitro. However, such cells showed significantly less cytostatic activity on a per cell basis than highly activated macrophages obtained from Corynebacterium parvum-immunized mice. Furthermore, this cytostatic activity declined as the infection progressed. Mitogen-induced transformation of splenic lymphocytes was also suppressed in the presence of adherent PM and SM from leprous mice. PM from leprous mice showed significantly less activity than PM from C. parvum-immunized mice in terms of suppression of lymphocyte transformation. Moreover, PM from leprous mice treated with C. parvum or sodium thioglycollate broth demonstrated significantly less ability to suppress lymphocyte transformation than did PM from similarly treated normal mice or untreated leprous mice. These findings demonstrated that MLM infection stimulates the mononuclear phagocyte system but does not activated it to the extent that it confers enhanced resistance to MLM on the host.

BCG, Corynebacterium parvum or Mycobacterium leprae added to cultures of BCG-primed mouse spleen cells cause an enhanced primary antibody response in vitro.

A few weeks after mice were injected i.v. with 10(8) live Mycobacterium bovis, BCG, the antibody response of their spleen cells to SRBC in vitro was comparable with the response of cells from untreated mice. Addition of BCG organisms to the culture vessels resulted in enhanced antibody-forming cell (AFC) responses by the primed cells but not by the cells from the untreated mice. No evidence was found for a direct stimulation of B cells and cell depletion experiments suggested macrophages were directly involved. BCG added to the cultures up to 68 h after they were set up, but not later, still caused enhancement. No enhancement was found when DNP-Ficoll was used as antigen. The ability to stimulate the anti-SRBC response was not restricted to the organism used for priming. Enhancement was also found if C. parvum or M. leprae were added to BCG-primed cells and if BCG was added to C. parvum-primed cells. The relevance of the results to the search for a leprosy vaccine is discussed.

Phagosome/lysosome fusion: a possible prerequisite for the enhancement of antibody responses in vitro by BCG, Mycobacterium leprae and Corynebacterium parvum.

Primary in vitro antibody responses to SRBC were suppressed in cultures prepared from the spleens of CBA mice injected i.v. 20 days previously with 10(8) liver BCG. In contrast, cultures prepared from mice injected with dead BCG showed enhanced responses. In vitro spleen cell responses of the mice had returned to normal levels 4--6 weeks after their injection, but if dead BCG, M. leprae or C. parvum was added to the cultures, responses were enhanced. The enhancing effect of the added bacteria could be removed by adding also suramin, a drug known to inhibit in vitro fusion of lysosomes with phagosomes. It is suggested that the different in vivo effects of live and dead BCG may relate to differences in their handling by macrophages and more especially that the enhanced antibody forming cell response seen in the restimulated cultures of spleen cells from BCG primed mice, depends upon efficient intracellular fusion of lysosomes with the phagosomes containing the added dead bacteria.