CD4+ T-lymphocytes in human saccular intracranial aneurysm walls are associated with aneurysm rupture

Chronic inflammation in saccular intracranial aneurysm (sIA) walls is associated with wall rupture. Previous studies have shown an association between macrophages and CD3+ T-lymphocytes with sIA wall degeneration and rupture but the roles of T-lymphocyte subtypes and B-lymphocytes are poorly understood. Here, cyclic multiplexed immunofluorescent staining was used to investigate the presence of T-lymphocytes helper CD4+ and cytotoxic CD8+ T-lymphocytes and CD20+ B-lymphocytes in 16 unruptured and 20 ruptured sIA walls. The sIA walls contained both CD4+ (n = 25/35) and CD8+ (n = 21/35) subtypes. There was a greater density of CD4+ T-lymphocytes (median 7, range 0-642 cells/mm2) vs CD8+ T-lymphocytes (median 1, range 0-30 cells/mm2). The density of CD4+ T-lymphocytes was associated with wall rupture, the presence of an intraluminal thrombus and numbers of vascular and lymphatic neovessels. Additionally, the densities of CD20+ B- and CD4+ T-lymphocytes were associated with atherosclerosis- and inflammation-related changes, such as the accumulation of apolipoprotein B-100 and serum amyloid A, and densities of CD68+ and CD163+ macrophages. These findings suggest that CD4+ T-lymphocytes play a role in sIA rupture, and that CD4+ T- and CD20+ B-lymphocytes contribute to sIA wall inflammation, particularly in the presence of atherosclerotic changes.