Abstract
The phenotype and functions of monocyte-derived dendritic cells (DCs), generated upon stimulation with GMCSF and IFN-α, were investigated in pulmonary tuberculosis (TB). Patient INF-DC cultures were characterized by increased number of CD14+ cells, lowered level of CD25+ cells and increased expression of B7-H1. Besides, DCs produced enhanced levels of IL-6 and IL-10 and differed by reduced secretion of INF-γ and INF-α. Patient IFN-DCs had lower capacity to stimulate allogeneic T-cell proliferation and induce CD3+IFN-γ+ T cells but increased ability to activate CD3+IL-4+ T cells in mixed lymphocyte culture. The most pronounced increase of IL-10 production, as well as the decrease of allostimulatory activity and the alteration of T1/T2 stimulatory activity of DCs were registered in patients with low PPD-induced proliferative response. The data obtained evidence the tolerogenic phenotype of monocyte-derived IFN-DCs and the association of DC impairment with decreased antigen-specific T cell response in TB patients.
Highlights
Pulmonary tuberculosis (TB), caused by Mycobacterium tuberculosis, is still remaining one of the most widespread infectious diseases
In the present study we have characterized for the first time the phenotype and functions of monocyte-derived dendritic cells (DCs) generated in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interferon- α (IFN-α) from peripheral blood of TB patients, and have compared DCs in purified protein derivative (PPD)-anergic and PPD-reactive patients
Our findings revealed that patient DCs had an increased CD14 and decreased CD25 expression indicating an impairment of differentiation and activation/maturation of patient DCs
Summary
Pulmonary tuberculosis (TB), caused by Mycobacterium tuberculosis, is still remaining one of the most widespread infectious diseases. Pathogenesis and disease course are in part determined by immune system impairments by the defective antigenspecific T-cell response. The deficiency of antigen-specific response in patients with TB is manifested by skin test anergy to tuberculin purified protein derivative (PPD), as well as decrease of T-cell proliferation and interferon-γ (IFN-γ) production in PPD-stimulated cultures [1]. The monocytes may differentiate into DCs when cultured with GM-CSF and interferon- α (IFN-α) [7,8] This way seems to be more natural, because IFN-α belongs to cytokines of the “first wave” that are produced in response to different pathogen stimuli and play the important role in TB [9,10]. IFN-α induced DCs (IFN-DCs) show the high engulfing activity, keep stable in the absence of cytokines and exceed the IL-4-DCs in migratory activity and ability to stimulate CD8 T-cells [7,11,12,13]
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