Resistance to Mycobacterium lepraemurium is correlated with the capacity to generate macrophage activating factor(s) in response to mycobacterial antigens in vitro

The kinetics of cell-mediated immunity developed during the course of Mycobacterium lepraemurium infection were determined in resistant (C57BL) and susceptible (BALB/c) mice. Control of M. lepraemurium growth following footpad infection was T-cell dependent in C57BL mice as shown by the finding that T-cell deprived mice had enhanced bacterial counts in the footpad. In contrast, T-cell deprivation did not significantly alter the course of infection in BALB/c mice. However a T-cell dependent inflammatory response, resulting in an increase in size of the infected footpad, occurred in both strains, although it developed slightly later in BALB/c mice. Cells isolated from the lymph nodes, draining the infected foot-pads, were assayed for their proliferative responses to heat-killed M. lepraemurium (HK-MLM) antigens. Although lymph node cells from both mouse strains proliferated to HK-MLM early in the infection (1-2 weeks) both C57BL and BALB/c mice developed diminished in vitro proliferative reactivity within 4-6 weeks post-infection. Supernatants derived from cultures of lymph-node cells that had been stimulated with concanavalin A (Con A) or HK-MLM antigens, were assayed for the presence of macrophage-activating factor (MAF) activity using a tumour cytostasis assay and interferon (IFN) activity using a viral growth inhibition assay. Significantly higher levels of MAF and IFN were found in culture supernatants deprived from HK-MLM stimulated lymph-node cells from infected C57BL mice than from BALB/c mice during the first 8 weeks of infection. However, cells from infected mice of both strains produced similar amounts of both MAF and IFN in response to Con A.