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Impairments of Antigen-Presenting Cells in Pulmonary Tuberculosis.

Sakhno LV, Shevela EY, Tikhonova MA, Nikonov SD, Ostanin AA, Chernykh ER - J Immunol Res (2015)

Bottom Line: We revealed the distinct impairments in patient APC functions.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 possible role of APC impairments in reducing the antigen-specific T-cell response to M. tuberculosis was discussed.

View Article: PubMed Central - PubMed

Affiliation: Research Institute of Clinical Immunology, Russian Academy of Medical Sciences (RAMS), Siberian Branch (SB), Yadrintsevskaya Street 14, Novosibirsk 630099, Russia.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Surface antigen expression on circulating monocytes obtained from peripheral blood of TB patients (a), PPD-reactive (b) and PPD-anergic (c) TB patients. Open histogram represents stained cells (patient Mo) and the filled histogram represents isotype specific control.
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fig1: Surface antigen expression on circulating monocytes obtained from peripheral blood of TB patients (a), PPD-reactive (b) and PPD-anergic (c) TB patients. Open histogram represents stained cells (patient Mo) and the filled histogram represents isotype specific control.

Mentions: Phenotypic analysis of freshly isolated monocytes (Table 1, Figure 1) revealed that monocytes from TB patients had a lower number of HLA-DR+ and CD86+ cells. Monocytes obtained from both PPD-reactive and PPD-anergic patients showed a decrease in HLA-DR and CD86 expression. Besides, TB patients demonstrated a significant increase in CD14+CD16+ monocytes, the level of which on average twice exceeded that of healthy subjects. The most pronounced increase in CD14+CD16+ monocytes was revealed in the PPD-anergic patients. The elevated rate (>17%) of CD14+CD16+ cells in this group (62%, 16/26) was observed twice oftener than among patients with the undiminished proliferative MNC response to PPD (26%, 10/39, PTMΦ = 0.04).


Impairments of Antigen-Presenting Cells in Pulmonary Tuberculosis.

Sakhno LV, Shevela EY, Tikhonova MA, Nikonov SD, Ostanin AA, Chernykh ER - J Immunol Res (2015)

Surface antigen expression on circulating monocytes obtained from peripheral blood of TB patients (a), PPD-reactive (b) and PPD-anergic (c) TB patients. Open histogram represents stained cells (patient Mo) and the filled histogram represents isotype specific control.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4539175&req=5

fig1: Surface antigen expression on circulating monocytes obtained from peripheral blood of TB patients (a), PPD-reactive (b) and PPD-anergic (c) TB patients. Open histogram represents stained cells (patient Mo) and the filled histogram represents isotype specific control.
Mentions: Phenotypic analysis of freshly isolated monocytes (Table 1, Figure 1) revealed that monocytes from TB patients had a lower number of HLA-DR+ and CD86+ cells. Monocytes obtained from both PPD-reactive and PPD-anergic patients showed a decrease in HLA-DR and CD86 expression. Besides, TB patients demonstrated a significant increase in CD14+CD16+ monocytes, the level of which on average twice exceeded that of healthy subjects. The most pronounced increase in CD14+CD16+ monocytes was revealed in the PPD-anergic patients. The elevated rate (>17%) of CD14+CD16+ cells in this group (62%, 16/26) was observed twice oftener than among patients with the undiminished proliferative MNC response to PPD (26%, 10/39, PTMΦ = 0.04).

Bottom Line: We revealed the distinct impairments in patient APC functions.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 possible role of APC impairments in reducing the antigen-specific T-cell response to M. tuberculosis was discussed.

View Article: PubMed Central - PubMed

Affiliation: Research Institute of Clinical Immunology, Russian Academy of Medical Sciences (RAMS), Siberian Branch (SB), Yadrintsevskaya Street 14, Novosibirsk 630099, Russia.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus