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https://doi.org/10.14300/mnnc.2020.15077

Features of cytotoxic immunophenotyping of macrophages in fibro-cavernous pulmonary tuberculosis

[Experimental medicine]
Elena Petrovna Golubinskaya; Julianna Arkadevna Yermola; Anatoly Vladimirovich Kubyshkin; Alina Vitalevna Gerashchenko; Tatyana Vadimovna Kramar;

Fragments of the lungs of 84 patients with fibrocavernous tuberculosis (FCT) with verified isolation of mycobacteria (FCT-MBT+) and 79 patients with FCT without bacterial excretion (FCT-MBT–) were studied. Immunoprofiling of lung tissue cell populations with markers of type 1 T-helpers and cytotoxic lymphocytes made it possible to determine a pool of epithelioid cells with a large vesicular nucleus of a rounded-oval shape, demonstrating a positive cytoplasmic reaction for both CD4 and CD8 receptors, exclusively in patients with active bacterial excretion. Localization corresponded to intact lung tissue at the border of the cavity resection and pericavernous areas of emphysema. Groups of such cells were visualized in the lumen of the alveoli or single cells in the «niches» of the epithelial lining. Comparison with routine staining with hematoxylin and eosin, as well as verification with the macrosialin marker CD68, proved the histiocytic origin of this cell population. At the same time, CD68+, CD4+, CD8+showed a negative reaction with VEGF-A, which excluded their belonging to functional type 2 macrophages with remodeling activity in relation to lung tissue. Analysis of IHC reactions with a marker of irreversible induction of apoptosis in the macrophage pool showed that Caspase-3 expression was visualized in all CD68+VEGF-A– macrophages. However, the intensity of the cytoplasmic reaction was most pronounced in the zone of specific granulation tissue of functional type 1 macrophages and in the pericavernous clusters of CD68+, CD4+, CD8+cells. It was shown that IHC identification of a population of macrophages with a cytotoxic immunophenotype (CD68+, CD4+, CD8+) in the lung tissue is a diagnostic and prognostic indicator of PCT activation and dissemination.

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Keywords: tuberculosis, ICH, T-lymphocytes, macrophage