ИСТИНА

The most widely applied vaccine in the world is the Mycobacterium bovis-derived bacillus Calmette-Guérin (BCG), which is used for exactly one hundred years to defend humans against tuberculosis (TB). Important issues regarding its highly variable performance in different populations are possible influence of host genetics and remarkable antigenic differences between attenuated M. bovis BCG and virulent M. tuberculosis strains circulating over the globe. Previously, our laboratory described an unusual phenotype of the mouse strain B10.M, carrying the H2f allelic variant of the H2 complex: the lack of BCG protective effect against subsequent challenge with virulent M. tuberculosis H37Rv. Congenic of mice of the B10 strain, carrying the H2b allelic variant of the H2 complex, demonstrated a normal level of the BCG protective effect. Thus, we compared vaccinated and non-vaccinated congenic mice of the two strains regarding post-challenge survival time, CFU counts in the lungs, T lymphocyte recognition of mycobacterial antigens and capacity to produce IFN-γ in response to specific and non-specific stimulation via T cell receptor. Our results show that T cells of B10.M mice are specifically defective for IFN-γ production in spleens and lungs in response to prolonged stimulation with mycobacterial antigens during chronic infection. However, immunologic recognition of these antigens was unaltered, as well as the capacity to secrete IFN-γ after non-specific signaling via T cell receptor following anti-CD3 antibodies stimulation. A defect in IFN-γ production might be due to the events that occur at the late phases of chronic infection and rather depend not upon prior BCG vaccination, but specific T cell immune exhaustion during a long-lasting course of the disease. (B10.M x B10)F1 hybrids displayed the phenotypes close to those displayed by B10 mice, demonstrating the dominant inheritance of the H2b haplotype.