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

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, 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.

Single-cell transcriptome analysis reveals the cellular atlas of human intracranial aneurysm and highlights inflammation features associated with aneurysm rupture

“…Astounding number of immune cells were identified in both unruptured and ruptured IA tissues, consistent with previous histology-based findings 4,5,50 . Immune cells including T and B lymphocytes, monocyte/macrophage, neutrophil, and to a lesser extent NK cell, mast cell, etc.…”

“…Immune cells including T and B lymphocytes, monocyte/macrophage, neutrophil, and to a lesser extent NK cell, mast cell, etc. are involved in IA rupture 10,41,50,51 . Particularly, monocyte/macrophages are widely present in IA tissues and can be found at an early stage of the disease 4,10,41 .…”

Decoding the Cell Atlas and Inflammatory Features of Human Intracranial Aneurysm Wall by Single‐Cell RNA Sequencing

“…Lymphocytes are present in normal and aneurysmal vessel walls, 7 , 50 while their role remains less understood. Herein, the lymphocytes were assigned as T cells ( CD3E , CD3G ), 51 B cells ( CD79A , MS4A1 ), 52 and NK cells ( KLRF1 , KLRD1 ) 20 manually (Figure 1C ).…”

Eomesodermin‐expressing type 1 regulatory (EOMES+Tr1)‐like T cells: Basic biology and role in immune‐mediated diseases

“…EOMES + Tr1‐like cells are in general enriched in inflamed tissues and play key roles in GvHD, IBDs, SLE, and in cancer. It seems likely that they are also involved in other pathologies, such as stroke [91] and organ‐specific autoimmune diseases [87].…”