The resistance of C57BL/6 mice to subcutaneous infection with Mycobacterium lepraemurium is dependent on both T cells and other cells of bone marrow origin.

Thymectomized or sham-thymectomized C57BL/6 mice were irradiated and reconstituted with either C57BL/6 bone marrow cells or bone marrow cells from H-2 matched BALB/B mice. The ability to limit organism multiplication at the site of infection in response to a moderate dose of Mycobacterium lepraemurium is shown to be T-cell mediated and not dependent on the type of bone marrow cells used for reconstitution. Dissemination of the organisms on the other hand appeared to be dependent on both T cells and cells of bone marrow origin.

Role of the major histocompatibility complex in resistance and granuloma formation in response to Mycobacterium lepraemurium infection.

Resistance to a subcutaneous infection with a moderate dose of Mycobacterium lepraemurium was investigated in C57BL/6 mice and in three congenic strains with the BALB background (BALB/c, BALB/B, and BALB/K). Resistance after 10 weeks of infection was found not to be linked to the major histocompatibility complex. The ability to develop a delayed hypersensitivity response to an ultrasonicate of M. lepraemurium was associated with the background genes, and this ability had no influence on resistance to M. lepraemurium. Granuloma formation at the infection site in the early stages appeared to be linked to the H-2b haplotype. The types of cells involved in the granulomas were also investigated.

The histopathology of tissues in "resistant" and "susceptible" strains of mice infected with a moderate dose of Mycobacterium lepraemurium.

A systematic study by light and electron microscopy of tissues from BALB/c and C57BL/6 mice infected subcutaneously with 10(7) Mycobacterium lepraemurium organisms was carried out at various times throughout the infection. The relatively resistant C57BL/6 mice had an earlier inflammatory response at the site of the infection than did the susceptible BALB/c mice. The infiltration in the former strain contained fibroblast-like cells and epithelioid cells early on in the infection. Few lymphocytes were observed in both strains throughout the infection. The spread of acid-fast bacilli was slower in the resistant strain (C57BL/6). The findings indicated that the rate of cellular infiltration at the infection site and the nature of the cells in the infiltration may determine the outcome of this infection.

H-2 linkage control of resistance to subcutaneous infection with Mycobacterium lepraemurium.

The H-2 linkage of the gene or genes controlling resistance to subcutaneous infection with 10(7) Mycobacterium lepraemurium organisms was investigated by using H-2 congenic strains on BALB and B10 backgrounds. Resistance was assessed by counting the organisms present at the infection site in the footpad and in the draining (right popliteal) lymph node 20 weeks after infection. When mice of BALB and B10 backgrounds with the same H-2 haplotype were compared, the BALB mice were always more susceptible. However, BALB/K (H-2k) mice were more susceptible than BALB/B (H-2b) mice, and BALB/B mice were more susceptible than BALB/c (H-2d) mice. There was no detectable difference in the resistance of B10.D2/n (H-2d) mice and B10 (H-2b) mice, but B10.BR (H-2k) mice were more susceptible than mice of the other two B10 strains. BALB/K was the only strain in which a high proportion of mice showed significant dissemination of organisms to the liver and spleen.

Differences in cell-mediated immune responses of 'high-resistance' and 'low-resistance' mice to a nonpathogenic mycobacterium.

The kinetics of the footpad response of bacillus Calmette-Guérin (BCG)-infected mice to soluble BCG antigens were compared in two strains of mice with different degrees of susceptibility to Mycobacterium lepraemurium. For the first 21 days the responses of the 'high-resistance' C57BL and the 'low-resistance' BALB/c to the nonpathogenic BCG were similar to that produced when the pathogenic mycobacterium was used. After 4 weeks the kinetics of the BALB/c mice changed and resembled that of the C57BL mice. The change in kinetics was compared with circulating antimycobacterial antibody levels and the response of draining lymph node cells in the antigen-specific lymphocyte transformation test. A dissociation was found between the kinetics of the delayed footpad response and the lymphocyte transformation response. Since both strains of mice are equally resistant to BCG, it appears that the delayed footpad response cannot be used as an indicator of host resistance in all mycobacterial infections.

A lack of correlation between antigen-specific cellular reactions and resistance to Mycobacterium lepraemurium infection in mice.

Following infection subcutaneously in the footpad with 10(7) Mycobacterium lepraemurium organisms C57BL mice were able to limit multiplication of organisms at the infection site for the 6 months studied and to limit organism spread to the draining lymph node. Large numbers of organisms were present in the footpad and draining lymph node of BALB/c mice at 6 months. In spite of this difference in local immunity the changes in cellular reactivity to specific antigen as assessed by the delayed footpad response and the in vitro proliferative response of draining lymph node cells were similar in the two strains over the time studied.