Adaptive and Innate Immune Cells in Fetal Human Cytomegalovirus-Infected Brains

Adaptive and Innate Immune Cells in Fetal Human Cytomegalovirus-Infected Brains

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Background: The understanding of the pathogenesis of cytomegalovirus (CMV)-induced fetal brain lesions is limited.We aimed to quantify adaptive and innate immune cells and CMV-infected cells in fetal brains with various degrees of brain damage.Methods: In total, 26 archived embedded fetal brains were studied, of which 21 were CMV-infected and classified in severely affected (n = 13) and moderately affected (n = 8), and 5 were uninfected controls.The respective magnitude of infected cells, immune cells (CD8+, B cells, plasma cells, NK cells, and macrophages), and expression of immune checkpoint receptors (PD-1/PD-L1 and LAG-3) were measured by immunochemistry and quantified D-3 by quantitative imaging analysis.Results: Quantities of CD8+, plasma cells, NK cells, macrophages, and HCMV+ cells and expression of PD-1/PD-L1 and LAG-3 were significantly higher in severely affected than in moderately affected brains (all p values < 0.

05).A strong link between higher number of stained cells for HCMV/CD8 and PD-1 and severity of brain lesions was found by component analysis.Conclusions: The higher expression Idler Pulleys of CD8, PD-1, and LAG-3 in severely affected brains could reflect immune exhaustion of cerebral T cells.These exhausted T cells could be ineffective in controlling viral multiplication itself, leading to more severe brain lesions.The study of the functionality of brain leucocytes ex vivo is needed to confirm this hypothesis.