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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

The spontaneous intracellular expression of TNF-α and IL-10 in donor (n = 8) and TB patient (n = 8) circulating CD14+ monocytes. The data are presented as M ± S.E. *PU < 0.05 (Mann-Whitney U-criterion) between healthy donors and TB patients.
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fig2: The spontaneous intracellular expression of TNF-α and IL-10 in donor (n = 8) and TB patient (n = 8) circulating CD14+ monocytes. The data are presented as M ± S.E. *PU < 0.05 (Mann-Whitney U-criterion) between healthy donors and TB patients.

Mentions: An evaluation of intracellular cytokine expression showed that monocytes from TB patients were characterized by a 3-fold decrease of TNF-α-secreting cells and a 6-fold increase of IL-10 secreting cells as compared to monocytes from healthy subjects (Figure 2). What is more, there appeared to exist an inverse correlation (rS = −0.62, PS < 0.01; n = 19) between the numbers of CD14+CD16+ cells and TNF-α+ monocytes.


Impairments of Antigen-Presenting Cells in Pulmonary Tuberculosis.

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

The spontaneous intracellular expression of TNF-α and IL-10 in donor (n = 8) and TB patient (n = 8) circulating CD14+ monocytes. The data are presented as M ± S.E. *PU < 0.05 (Mann-Whitney U-criterion) between healthy donors and TB patients.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig2: The spontaneous intracellular expression of TNF-α and IL-10 in donor (n = 8) and TB patient (n = 8) circulating CD14+ monocytes. The data are presented as M ± S.E. *PU < 0.05 (Mann-Whitney U-criterion) between healthy donors and TB patients.
Mentions: An evaluation of intracellular cytokine expression showed that monocytes from TB patients were characterized by a 3-fold decrease of TNF-α-secreting cells and a 6-fold increase of IL-10 secreting cells as compared to monocytes from healthy subjects (Figure 2). What is more, there appeared to exist an inverse correlation (rS = −0.62, PS < 0.01; n = 19) between the numbers of CD14+CD16+ cells and TNF-α+ monocytes.

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