Journal Article

Deep Phenotyping of T-Cells Derived From the Aneurysm Wall in a Pediatric Case of Subarachnoid Hemorrhage

Ortolano, Fabrizio, Abrignani, Sergio, Vasco, Chiara, Carbonara, Marco, Geginat, Jens, Zoerle, Tommaso, Clemente, Francesca, Galeota, Eugenia, Stocchetti, Nino, Moschetti, Giorgia, Pluderi, Mauro, Zanier, Elisa R, Locatelli, Marco

2022

Overview

Intracranial aneurysms (IAs) are very rare in children, and the characteristics of the T-cells in the IA wall are largely unknown. A comatose 7-years-old child was admitted to our center because of a subarachnoid hemorrhage due to a ruptured giant aneurysm of the right middle cerebral artery. Two days after the aneurysm clipping the patient was fully awake with left hemiparesis. T-cells from the IA wall and from peripheral blood of this patient were analyzed by multi-dimensional flow cytometry. Unbiased analysis, based on the use of FlowSOM clustering and dimensionality reduction technique UMAP, indicated that there was virtually no overlap between circulating and tissue-infiltrating T-cells. Thus, naïve T-cells and canonical memory T-cells were largely restricted to peripheral blood, while CD4 - CD8 - T-cells were strongly enriched in the IA wall. The unique CD4 + , CD8 + and CD4 - CD8 - T-cell clusters from the IA wall expressed high levels of CCR5, Granzyme B and CD69, displaying thus characteristics of cytotoxic and tissue-resident effector cells. Low Ki67 expression indicated that they were nevertheless in a resting state. Among regulatory T-cell subsets, Eomes + Tr1-like cells were strongly enriched in the IA wall. Finally, analysis of cytokine producing capacities unveiled that the IA wall contained poly-functional T-cells, which expressed predominantly IFN-γ, TNF and IL-2. CD4 + T-cells co-expressed also CD40L, and produced some IL-17, GM-CSF and IL-10. This report provides to our knowledge the first detailed characterization of the human T-cell compartment in the IA wall.

• Publisher: Frontiers Media SA,Frontiers Media S.A
• Subject: Aneurysm / Aneurysms / CD4 antigen / CD40L protein / CD69 antigen / CD8 antigen / Cells / Cytokines / Cytotoxicity / Effector cells / Flow cytometry / Granulocyte-macrophage colony-stimulating factor / Granzyme B / Hemodynamics / Hemorrhage / Immunological memory / Immunology / Interleukins / intracranial aneurysm / Lymphocytes / Lymphocytes T / Memory cells / Paresis / Pathogenesis / Pediatrics / Peripheral blood / phenotype / Software / subarachnoid haemorrhage / Subarachnoid hemorrhage / T-cells / Tomography / γ-Interferon