ИСТИНА

Tuberculosis (TB) pathogenesis is multistage, highly complex sequence of events involving manytypes of cells. Earlier our laboratory demonstrated that a high-dose vaccination with bacillus Calmette-Guerin (BCG) before Mycobacterium tuberculosis H37Rv challenge significantly prolonged survivaltimes of genetically resistant and susceptible inbred mice, except the strain B10.M (H-2f). In thepresent study we applied a more relevant TB model based upon aerosol infection of B10.M and H2-congenic B10 (H-2b) control mice, which readily respond to BCG vaccination after intravenouschallenge. It was shown that spleen and lung T cells of B10.M mice are defective for IFN-γ productionin response to prolonged stimulation with mycobacterial antigens during chronic infection. However,immunologic recognition of these antigens was unaltered (proliferative response), as was the capacityof secrete IFN-γ after non-specific signaling via T cell receptor (anti-CD3 response). We demonstratethat lung T cells from infected B10.M mice produce significantly lower amounts of IFN-γ in response tomycobacterial antigens compared to B10 cells, and that this phenotype does not depend upon BCGvaccination. These results suggest that immune response in infected lungs of B10.M mice may be lessTh1-biased. However, further research is needed to answer the question whether “fail-of-vaccination”phenotype of B10.M mice is due to abnormal memory T cell development or exhaustion of IFN-γ-producing T cell pool, perhaps, because of activation-induced cell death.Animal House of the CIT is supported by the Federal Program AAAA-A16-116032560061-9. Thisstudy was supported by the RSF grant 18-45-04015.