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, naive 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-gamma, 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.

Deep Phenotyping of T-Cells Derived From the Aneurysm Wall in a Pediatric Case of Subarachnoid Hemorrhage / G. Moschetti, C. Vasco, F. Clemente, E. Galeota, M. Carbonara, M. Pluderi, M. Locatelli, N. Stocchetti, S. Abrignani, E.R. Zanier, F. Ortolano, T. Zoerle, J. Geginat. - In: FRONTIERS IN IMMUNOLOGY. - ISSN 1664-3224. - 13:(2022), pp. 866558.1-866558.12. [10.3389/fimmu.2022.866558]

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

G. Moschetti;C. Vasco;M. Carbonara;M. Pluderi;M. Locatelli;N. Stocchetti;S. Abrignani;F. Ortolano;T. Zoerle;J. Geginat
2022

Abstract

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, naive 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-gamma, 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.
T-cells; flow cytometry; intracranial aneurysm; phenotype; subarachnoid haemorrhage; CD8-Positive T-Lymphocytes; Child; Humans; T-Lymphocyte Subsets; Aneurysm, Ruptured; Intracranial Aneurysm; Subarachnoid Hemorrhage
Settore MED/04 - Patologia Generale
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/943361
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