[Characteristics of A-interferon-generated dendritic cells in patients with pulmonary tuberculosis].

The phenotype of the dendritic cells (DC) generated from the adhesion fraction of mononuclear cells in the presence of GM-CSF and alpha-interferon was studied in patients with pulmonary tuberculosis. Despite the absence of significant differences in the count of mature CD83+DCs in the groups of patients (n = 38) and healthy donors (n = 30), elevated CD14(+)-monocyte levels and few activated CD25(+)-DCs were indicative of the impaired process of DC maturation/generation in patients with pulmonary tuberculosis, particularly in a subgroup of patients with a low T-cell proliferative response against PPD (PPD-anergy, n = 10). The patients with tuberculosis showed the lower relative levels of CD11c(-)-CD123(+)-DC and the normal levels of myeloid CD11c(+)D123(-)DCs. However, in patients with PPD-anergy, the content of myeloid CD11c(+)CD123(-)-DCs was significantly higher than that in PPD-reactive patients. Moreover, the patients with PPD-anergy were characterized by the elevated peripheral blood levels of CD14+CD16(+)-monocytes, which was associated with the high suppressive activity of monocytes (r(s) = 0.53; p < 0.05). The impaired process of DC generation/maturation in patients with pulmonary tuberculosis is believed to be associated with the changes in the phenotypic and functional properties of monocytes and to be a cause of an inadequate antigen-specific response in tuberculous infection.

[Interleukin-2 in the correction of T-cell anergy in patients with pulmonary tuberculosis].

The clinical and immunomodulating effects of lymphotropic administration of interleukin-2 (IL-2) were studied in the combine treatment of patients with pulmonary tuberculosis. The patients with tuberculosis were shown to have the low levels of monocytes with the intracellular expression of tumor necrosis factor-alpha (TNF-alpha) and the high count of CD14+ CD16+ monocytes with the intracellular expression of IL-10. The changes in the monocytic link were most pronounced in patients with PPD-induced anergy appeared as the low proliferation and production of alpha-interferon (alpha-INF). During clinical trials, 19 patients received tuberculostatic therapy in combination with IL-2 (Roncoleukin) (a study group) whereas 16 patients had tuberculostatic therapy alone (a control group). The administration of Roncoleukin statistically significant increased a proliferative response to PPD and normalized the count of CD14+ CD16+ monocytes with anti-inflammatory and immunosuppressive activities. The restoration of a PPD response was recorded more frequently in the study group than in the control one (75% vs 30%; p = 0.045). The magnitude of positive X-ray changes was also higher in the study group than in the control one (63% vs 25%; p = 0.026). The findings suggest the clinical and immunomodulating effects of IL-2 (Roncoleukin) in the combined therapy for tuberculosis.

[T-cellular energy deficiency in the pathogenesis of immunodeficiency in pulmonary tuberculosis]. / T-kletochnaia anergiia v patogeneze immunnoi nedostatochnosti pri tuberkuleze legkikh.

The phenotypic and functional properties of T cells were evaluated in patients with tuberculin anergy and a possible role of anergic T cells in the development of immune deficiency in pulmonary tuberculosis (PT) was studied. The profound decrease (more than 50%) depressed T-cell proliferation in PPD-stimulated cultures was shown to be recorded in 44% (59/134) patients with PT. PPD hyporesponsiveness was associated with the low proliferation of anti-CD3 and SEB-stimulated proliferation of a healthy donor's mononuclear cells evidencing the enlargement of anergic T cells with a suppressive activity in PT. A PPD-stimulated response in healthy donors was under the negative control of CG25-positive cells. In the PPD-anergic patients, there was a significant increase in CD4+CD25+ T cells that were inversely correlated with the PPD-induced proliferative response. The development of tuberculin anergy was more pronounced in patients with drug resistance. The intensity of a PPD-stimulated response in patients with tuberculin anergy may be restored in the presence of exogenous interleukin-2.

[T cell subsets undergoing apoptosis and anergy in patients with pulmonary tuberculosis]. / Subpopuliatsionnaia prinadlezhnost' T-kletok, podverzhennykh anergii i apoptozu u bol'nykh tuberkulezom legkikh.

T-cell apoptosis and anergy as possible causes of impaired antigen specific responses and their subpopulation targets in patients with pulmonary tuberculosis were investigated. A decrease in PPD-stimulated proliferative responses were revealed in 43% of the examinees. The impaired PPD response was shown to be associated with both increased lymphocytic apoptosis and the arrest of cell cycle progression. CD4 and CHD8 T cells underwent apoptosis in PPD-stimulated cultures. Whereas a moderate apoptosis of CD4 cell could occur in PPD-reactive patients, accelerated apoptosis of CD8 cells developed only in PPD-unresponsive group. Both T-cell subpopulations displayed a decreased count of cells in S,G2/M phases of a cell cycle. Similar to apoptosis, the anergy of CD8 T cells was typical of PPD-unresponsive patients. Elevated apoptosis and anergy of CD4 and CD8 T cells in vitro were accompanied by a decline in the proportion of T cells and their subpopulations in patients with impaired PPD responses.

[Immunomodulating effect of locoregional cytokine therapy in patients with pulmonary tuberculosis]. / Immunokorrigiruiushchii éffekt lokoregional'noi tsitokinoterapii u bol'nykh tuberkulezom legkikh.

The immunomodulating effect of local and regional cytokine therapy was studied in patients with different forms of pulmonary tuberculosis. The signs of immunosuppression either preserve or progress with tuberculostatic chemotherapy (a control group). The inclusion of cytokine therapy into a treatment regimen for patients with pulmonary tuberculosis (an experimental group) assures complete correction of immune disorders in 30% of patients, as manifested by a significant increase in the absolute count of T lymphocytes, in the relative content of CD8 cells and monocytes with HLA-DR antigen expression. The most pronounced effect was achieved in patients with a fibrocavernous form of pulmonary tuberculosis. Immunological correction was accompanied by positive clinical and laboratory changes. Arrested intoxication, improved X-ray pattern of the lung, and ceased bacterial isolation were recorded in the patients. Positive clinical and immunological changes suggest that it is expedient to include local and regional cytokine therapy as part of treatment in patients with pulmonary tuberculosis.