SUMMARYProtective immunity against infection with Mycobacterium tuberculosis is imparted by T cells rather than antibodies, but B cells can play a role as antigen-presenting cells and in granuloma formation. We re-evaluated the role of B cells in the course of tuberculous infection in ¹ -chain knock-out (Ig ÿ ) mice. Surprisingly, the organs of M. tuberculosis-infected Ig ÿ mice were found to have three-to eight-fold elevated counts of viable bacilli compared with normal littermates at 3-6 weeks post-infection. Splenic interferon-gamma responses to whole antigen were unimpaired, whilst proliferation to certain mycobacterial peptides was found to be diminished. However, bacille Calmette-Guérin (BCG) vaccination significantly reduced the infection in Ig ÿ mice. The mechanisms by which B cells can influence primary tuberculous infection need further study.

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A number of subunit-based vaccine candidates have recently begun to erode the exclusive position of Mycobacterium bovis bacillus Calmette-Guérin (BCG), which gives unpredictable and highly variable protection against tuberculosis. In this paper we investigated the protective capacity of the 19,000 MW and 38,000 MW glyco-lipoproteins of M. tuberculosis expressed by recombinant vaccinia viruses in a mouse Mycobacterium tuberculosis infection model. Both proteins were expressed at high levels by recombinant vaccinia-infected cells. In addition, two inoculations of C57B1/6 mice with either recombinant vaccinia virus significantly reduced the bacterial counts in the lungs of M. tuberculosis H37Rv-infected mice, when compared with the group infected with control virus. This is the first report of protection against tuberculous infection using recombinant vaccinia viruses with results that suggest that secreted glyco-lipoproteins in conjunction with the vaccinia vector represent suitable candidates for further vaccine-related studies.

Immunotherapy as an adjunct to chemotherapy is of interest for optimizing therapeutic regimens for tuberculosis. In this context, we investigated the influence and mode of action of glucosaminylmuramyl dipeptide (GMDP) in mouse experimental models. Intermittent injections of GMDP to Mycobacterium tuberculosis-infected mice reduced the viable bacilli in the lungs, but increased the counts in the spleens at 16 weeks, but not at earlier harvests after infection. Injections of GMDP selectively ameliorated also in the lungs the spontaneous relapse of infection following chemotherapy. The mode of GMDP action was examined in respect of superoxide anion production. The O^––₂ production by phorbol myristate-induced peritoneal macrophages in vitro was reduced by preinjection of mice with 100 μg of GMDP. Notably, this outcome contrasts and can also override the previously known enhancing effect of MDP on O^––₂ production. The inhibitory activity of GMDP became even more pronounced when testing macrophages from Mycobacterium bovis BCG-infected mice. However, these results do not explain readily the grounds for the contrasting effects of GMDP on the growth patterns of tubercle bacilli in the lungs and spleens. Although the observed effects on bacillary counts have been modest, such action of GMDP could represent a beneficial adjunct to suitably formulated chemotherapeutic regimens.