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Low Antigen-specific T-cell Response in Pulmonary Tuberculosis is Associated with Impaired Phenotype and Functions of Interferon-α Induced Dendritic Cells

Sakhno LV, Leplina OYu, Tikhonova MA, Shevela EYa, Nikonov SD, Zhdanov OA, Ostanin AA and Chernykh ER

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.