Impairments of Antigen-Presenting Cells in Pulmonary Tuberculosis.
The phenotype and functional properties of antigen-presenting cells (APC), that is, circulating monocytes and generated in vitro macrophages and dendritic cells, were investigated in the patients with pulmonary tuberculosis (TB) differing in lymphocyte reactivity to M. tuberculosis antigens (PPD-reactive versus PPD-anergic patients). We revealed the distinct impairments in patient APC functions. For example, the monocyte dysfunctions were displayed by low CD86 and HLA-DR expression, 2-fold increase in CD14(+)CD16(+) expression, the high numbers of IL-10-producing cells, and enhanced IL-10 and IL-6 production upon LPS-stimulation. The macrophages which were in vitro generated from peripheral blood monocytes under GM-CSF were characterized by Th1/Th2-balance shifting (downproduction of IFN-γ coupled with upproduction of IL-10) and by reducing of allostimulatory activity in mixed lymphocyte culture. The dendritic cells (generated in vitro from peripheral blood monocytes upon GM-CSF + IFN-α) were characterized by impaired maturation/activation, a lower level of IFN-γ production in conjunction with an enhanced capacity to produce IL-10 and IL-6, and a profound reduction of allostimulatory activity. The APC dysfunctions were found to be most prominent in PPD-anergic patients. The possible role of APC impairments in reducing the antigen-specific T-cell response to M. tuberculosis was discussed.
Research Institute of Clinical Immunology, Russian Academy of Medical Sciences (RAMS), Siberian Branch (SB), Yadrintsevskaya Street 14, Novosibirsk 630099, Russia.
Ludmila V
LV
Sakhno
Research Institute of Clinical Immunology, Russian Academy of Medical Sciences (RAMS), Siberian Branch (SB), Yadrintsevskaya Street 14, Novosibirsk 630099, Russia.
Ekaterina Ya
EY
Shevela
Research Institute of Clinical Immunology, Russian Academy of Medical Sciences (RAMS), Siberian Branch (SB), Yadrintsevskaya Street 14, Novosibirsk 630099, Russia.
Marina A
MA
Tikhonova
Novosibirsk Tuberculosis Clinical Hospital No. 1, Vavilova Street 14, Novosibirsk 630082, Russia.
Sergey D
SD
Nikonov
Research Institute of Clinical Immunology, Russian Academy of Medical Sciences (RAMS), Siberian Branch (SB), Yadrintsevskaya Street 14, Novosibirsk 630099, Russia.
Alexandr A
AA
Ostanin
Research Institute of Clinical Immunology, Russian Academy of Medical Sciences (RAMS), Siberian Branch (SB), Yadrintsevskaya Street 14, Novosibirsk 630099, Russia.
Elena R
ER
Chernykh
D000328:Adult; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism; D015415:Biomarkers; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000378:metabolism; D010641:Phenotype; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D014397:Tuberculosis, Pulmonary / Q000276:immunology* / Q000378:metabolism; D055815:Young Adult
D015415:Biomarkers; D016207:Cytokines