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 t...
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| Format: | Article |
| Language: | English |
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Wiley
2012-01-01
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| Series: | Clinical and Developmental Immunology |
| Online Access: | http://dx.doi.org/10.1155/2012/628635 |
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| author | Ludmila V. Sakhno Marina A. Tikhonova Tamara V. Tyrinova Olga Yu. Leplina Ekaterina Ya. Shevela Sergey D. Nikonov Oleg A. Zhdanov Alexander A. Ostanin Elena R. Chernykh |
| author_facet | Ludmila V. Sakhno Marina A. Tikhonova Tamara V. Tyrinova Olga Yu. Leplina Ekaterina Ya. Shevela Sergey D. Nikonov Oleg A. Zhdanov Alexander A. Ostanin Elena R. Chernykh |
| author_sort | Ludmila V. Sakhno |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-8dce6259c68c42fcb81e33acaa3cb9c3 |
| institution | OA Journals |
| issn | 1740-2522 1740-2530 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical and Developmental Immunology |
| spelling | doaj-art-8dce6259c68c42fcb81e33acaa3cb9c32025-08-20T02:09:41ZengWileyClinical and Developmental Immunology1740-25221740-25302012-01-01201210.1155/2012/628635628635Cytotoxic Activity of Dendritic Cells as a Possible Mechanism of Negative Regulation of T Lymphocytes in Pulmonary TuberculosisLudmila V. Sakhno0Marina A. Tikhonova1Tamara V. Tyrinova2Olga Yu. Leplina3Ekaterina Ya. Shevela4Sergey D. Nikonov5Oleg A. Zhdanov6Alexander A. Ostanin7Elena R. Chernykh8Research Institute of Clinical Immunology, Russian Academy of Medical Sciences (RAMS), Siberian Branch (SB), Novosibirsk 630099, RussiaResearch Institute of Clinical Immunology, Russian Academy of Medical Sciences (RAMS), Siberian Branch (SB), Novosibirsk 630099, RussiaResearch Institute of Clinical Immunology, Russian Academy of Medical Sciences (RAMS), Siberian Branch (SB), Novosibirsk 630099, RussiaResearch Institute of Clinical Immunology, Russian Academy of Medical Sciences (RAMS), Siberian Branch (SB), Novosibirsk 630099, RussiaResearch Institute of Clinical Immunology, Russian Academy of Medical Sciences (RAMS), Siberian Branch (SB), Novosibirsk 630099, RussiaNovosibirsk Tuberculosis Clinical Hospital No. 1, Novosibirsk 630099, RussiaNovosibirsk Tuberculosis Clinical Hospital No. 1, Novosibirsk 630099, RussiaResearch Institute of Clinical Immunology, Russian Academy of Medical Sciences (RAMS), Siberian Branch (SB), Novosibirsk 630099, RussiaResearch Institute of Clinical Immunology, Russian Academy of Medical Sciences (RAMS), Siberian Branch (SB), Novosibirsk 630099, RussiaThe 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.http://dx.doi.org/10.1155/2012/628635 |
| spellingShingle | Ludmila V. Sakhno Marina A. Tikhonova Tamara V. Tyrinova Olga Yu. Leplina Ekaterina Ya. Shevela Sergey D. Nikonov Oleg A. Zhdanov Alexander A. Ostanin Elena R. Chernykh Cytotoxic Activity of Dendritic Cells as a Possible Mechanism of Negative Regulation of T Lymphocytes in Pulmonary Tuberculosis Clinical and Developmental Immunology |
| title | Cytotoxic Activity of Dendritic Cells as a Possible Mechanism of Negative Regulation of T Lymphocytes in Pulmonary Tuberculosis |
| title_full | Cytotoxic Activity of Dendritic Cells as a Possible Mechanism of Negative Regulation of T Lymphocytes in Pulmonary Tuberculosis |
| title_fullStr | Cytotoxic Activity of Dendritic Cells as a Possible Mechanism of Negative Regulation of T Lymphocytes in Pulmonary Tuberculosis |
| title_full_unstemmed | Cytotoxic Activity of Dendritic Cells as a Possible Mechanism of Negative Regulation of T Lymphocytes in Pulmonary Tuberculosis |
| title_short | Cytotoxic Activity of Dendritic Cells as a Possible Mechanism of Negative Regulation of T Lymphocytes in Pulmonary Tuberculosis |
| title_sort | cytotoxic activity of dendritic cells as a possible mechanism of negative regulation of t lymphocytes in pulmonary tuberculosis |
| url | http://dx.doi.org/10.1155/2012/628635 |
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