A DEFICIENCY OF ANTIGEN-PRESENTING CELLS IN PATIENTS WITH PULMONARY TUBERCULOSIS

Abstract. The phenotype and functional properties of antigen-presenting cells (APCs: blood monocytes and in vitro generated macrophages/dendritic cells) were investigated in patients with pulmonary tuberculosis (TB, n = 192) with different levels of proliferative response to M. tuberculosis antigens (PPD-responsive vs PPD - anergic patients, n = 118 and 74, respectively). A functional deficiency of all 3 types of APCs was revealed in patients with TB. I.e., a monocyte disfunction was displayed by low CD86 and HLA-DR expression, 2-fold increase of CD14+CD16+ subset, high level of FasL+ and IL-10+ cells, and enhanced IL-10 and IL-6 production upon LPS-stimulation. The in vitro generated macrophages from blood monocytes challenged with GM-CSF, were characterized by shifted Th1/Th2 balance (down-regulated production of IFNγ and IL-18 combined with up-regulation of IL-6 and IL-10), and reduced allostimulatory activity in mixed lymphocyte culture. The dendritic cells were characterized by decrease of mature, activated CD25+ cells, low level of IFNγ production in conjunction with enhanced capacity to produce IL - 10 and IL-6, and profound reduction of functional (allostimulatory) activity. The APC disfunction of were most prominent in PPD-anergic patients. A possible role of APC disfunctions in disturbed antigen-specific T-cell response to M. tuberculosis is discussed.

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