T-helper 1-like subset selection in Mycobacterium bovis bacillus Calmette-Guérin-infected resistant and susceptible mice.
The Bcg gene has been shown to control natural resistance of mice to intravenous infection with low doses of Mycobacterium bovis (bacillus Calmette-Guérin; BCG). In the present study, we evaluated the impact of the Bcg gene on the development of T-cell reactivity during the early stages of infection. Congenic strains of mice, bearing 'r' and 's' alleles of the Bcg gene on B10.A and BALB/c backgrounds, were studied at different time-points for 2 weeks after infection. The in vitro proliferative response of spleen cells, induced by mycobacteria or concanavalin A, was depressed in the Bcgs mice compared to the Bcgr congenic mice 14 days after infection with 10(5) colony-forming units (CFU) of BCG. Polymerase chain reaction (PCR)-based methodology was used to compare the level of lymphokine gene expression in the spleens of infected congenic mice both ex vivo and after in vitro stimulation. In both cases, preferential expression of interferon-gamma (IFN-gamma), lymphotoxin, interleukin-2 (IL-2) and IL-2 receptor genes was observed. The lymphokine gene expression profiles indicated that T lymphocytes activated in the course of the BCG infection preferentially expressed the T-helper 1-specific pattern, irrespective of the allele of the Bcg gene. We showed that this bias in T-cell differentiation could not be attributed to either down-regulation of IL-4 gene expression or modulation of the macrophage co-stimulatory activity by live M. bovis BCG. We conclude that the mechanism of phenotypic expression of the Bcg gene resides in the differential ability of macrophages to be activated by lymphokines produced by protective T cells, rather than in the lack of these lymphokines in susceptible animals.
McGill Centre for the Study of Host Resistance, Montreal General Hospital Research Institute, Quebec, Canada.
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Kramnik
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Radzioch
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Skamene
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D002455:Cell Division / Q000235:genetics; D002478:Cells, Cultured; D005802:Genes, MHC Class II / Q000276:immunology; D007113:Immunity, Innate / Q000235:genetics; D008222:Lymphokines / Q000235:genetics; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D009163:Mycobacterium bovis / Q000276:immunology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D013154:Spleen / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology*
D000942:Antigens, Bacterial; D008222:Lymphokines; D012333:RNA, Messenger