Frequency of Mycobacterium tuberculosis-specific CD8+ T-cells in the course of anti-tuberculosis treatment.

摘要: Anti-tuberculosis drug treatment is known to affect the number, phenotype, and effector functionality of antigen-specific T-cells. In order objectively gauge Mycobacterium tuberculosis (MTB)-specific CD8+ T-cells at single-cell level, we developed soluble major histocompatibility complex (MHC) class I multimers/peptide multimers, which allow analysis without ex vivo manipulation or functional tests. We constructed 38 MHC multimers covering some most frequent alleles (HLA-A*02:01, A*24:02, A*30:01, A*30:02, A*68:01, B*58:01, C*07:01) pertinent a South African Zambian population, presenting following MTB-derived peptides: early expressed secreted antigens TB10.4 (Rv0288), Ag85B (Rv1886c), ESAT-6 (Rv3875), as well intracellular enzymes, i.e., glycosyltransferase 1 (Rv2957), 2 (Rv2958c), cyclopropane fatty acid synthase (Rv0447c). Anti-TB appeared impact on frequency multimer-positive T-cells, with general decrease after 6 months therapy. Also, reduction in total central memory T-cell frequencies, compartment CD45RA-CCR7+ was observed. discuss our findings basis differential dynamics MTB-specific MTB antigen load responses tuberculosis.