Cytotoxic activity of dendritic cells as a possible mechanism of negative regulation of T lymphocytes in pulmonary tuberculosis.
The PD-1/B7-H1-mediated induction of T cell apoptosis/anergy as a possible mechanism of immune response failure was studied in 76 patients with pulmonary tuberculosis (TB) with normal and low-proliferative response to antigens of M. tuberculosis (purified protein derivative (PPD)). It was revealed that dendritic cells (DCs), generated in vitro from patient blood monocytes with GM-CSF + IFN-α, were characterized by increased B7-H1 expression, upproduction of IL-10, and reducing of allostimulatory activity in mixed lymphocyte culture (MLC). Moreover, DCs of patients with TB were able to enhance T cell apoptosis and to block T-cell division in MLC. It was shown that neutralizing anti-PD1 antibodies significantly decreased the proapoptogenic/tolerogenic effect of DCs. Correlation analysis revealed a direct relationship between IL-10 production and level of B7-H1 expression in the general group of investigated patients. It was demonstrated that generation of healthy donor DCs in the presence of IL-10 led to an increase in the number of DCs-expressed B7-H1 molecule, DC proapoptogenic activity, and a decrease in their allostimulatory activity. Obviously, the revealed phenomenon of the PD-1/B7-H1-mediated pro-apoptogenic activity of DCs is clinically significant since the cytotoxic/tolerogenic potential of DCs is more pronounced in patients with PPD anergy.
Research Institute of Clinical Immunology, Russian Academy of Medical Sciences (RAMS), Siberian Branch (SB), Novosibirsk, Russia. lsahno53@mail.ru
Ludmila V
LV
Sakhno
Marina A
MA
Tikhonova
Tamara V
TV
Tyrinova
Olga Yu
OY
Leplina
Ekaterina Ya
EY
Shevela
Sergey D
SD
Nikonov
Oleg A
OA
Zhdanov
Alexander A
AA
Ostanin
Elena R
ER
Chernykh
D000293:Adolescent; D000328:Adult; D057134:Antibodies, Neutralizing / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology; D017209:Apoptosis / Q000276:immunology; D051017:Apoptosis Regulatory Proteins / Q000276:immunology; D060890:B7-H1 Antigen / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology / Q000494:pharmacology; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007371:Interferon-gamma / Q000276:immunology / Q000494:pharmacology; D016753:Interleukin-10 / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D009169:Mycobacterium tuberculosis / Q000276:immunology; D061026:Programmed Cell Death 1 Receptor / Q000276:immunology; D014397:Tuberculosis, Pulmonary / Q000276:immunology* / Q000628:therapy*; D055815:Young Adult
D057134:Antibodies, Neutralizing; D000942:Antigens, Bacterial; D051017:Apoptosis Regulatory Proteins; D060890:B7-H1 Antigen; C423236:CD274 protein, human; C508609:IL10 protein, human; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D016753:Interleukin-10; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor