Análise da presença de dano inespecífico mediado por células T CD8 no pulmão de pacientes com COVID-19
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Data
2022-08-12
Autores
Lopes, Paola de Oliveira
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Universidade Federal do Espírito Santo
Resumo
Patients who develop more severe symptoms of COVID-19 often present an acute inflammatory lung injury characterized by the presence of acute respiratory distress syndrome (ARDS). The lung epithelium is related to the presence of immune system cells with high inflammatory activity, mediated by cytokines production and cytotoxicity. Senescent cells accumulate in tissues during ageing, chronic stimulatory processes and infections. These cells present phenotypic and functional disorders, resulting in the inability to control pathogens, as well as tissue pathogenesis mediated through intense inflammatory activity. The latter favours the acquisition of natural killer cell receptors (NKRs) on CD8 T cells, and their ligands (NKRL) and other cell populations. In this work, using immunohistochemistry and immunofluorescence techniques using p16, we evaluated the presence of senescent cells in the lung injury of patients with fatal COVID-19. Our analyzes demonstrate diffuse alveolar damage (DAD) with intense inflammatory exudate in the intra-alveolar and interseptal regions. Compared to healthy controls, patients with COVID-19 showed an intense cellular inflammatory infiltrate, with an accumulation of CD8 T cells and senescent alveolar macrophages (CD68+). Complementary analyzes in patients' lungs demonstrate the presence of cells expressing the MICA/B ligand, which was significantly more associated with macrophages. Interesting, no differential expression was seen in lung epithelial cells (AE1AE3). The presence of cells expressing the NK cell receptor (NKG2D) was determined in the lung lesion, however, compared to healthy controls, we did not find its expression associated with infiltrating CD8 T lymphocytes. This suggests that possible damage mediated by nonspecific antigen activation of CD8 T cells may be mediated by other NK cell ligands. The results of this work contribute to a better understanding of the participation of senescence and the activity of NKRs expressed by senescent T cells in the immunopathogenesis of COVID-19.
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Imunopatologia , Senescência , Imunosenescência , Receptores de células natural killers (NKR) , Células T CD8