Photo Credit: Design Cells

The following is a summary of “Disordered Balance of T‐Cell Subsets in Arterial Tertiary Lymphoid Organs in Immunoglobulin G4–Related Vascular Disease,” published in the December 2023 issue of Cardiology by Kasashima et al.

Arterial/aortic tertiary lymphoid organs (ATLOs), identifiable by germinal centers, play a pivotal role in local arterial immune responses. Within these centers, T follicular helper cells (Tfh) manage immunoglobulin production and germinal center evolution, comprising subsets like Tfh1, Tfh2, and Tfh17. Another subset, T follicular regulatory (Tfr) cells, known for their regulatory function, migrate into germinal centers. This study focuses on Immunoglobulin G4 (IgG4)–related vascular diseases that often manifest as inflammatory aneurysms (IgG4‐related abdominal aortic aneurysms [IgG4‐AAAs]), featuring several ATLOs.

Researchers conducted comprehensive whole‐slide immunohistochemical image analysis on surgical samples from IgG4‐AAAs (n=21), non–IgG4‐related inflammatory AAAs (n=17), atherosclerotic AAAs (n=10), and Takayasu arteritis (n=5). In IgG4‐AAA, the study group observed numerous irregularly shaped ATLOs, housing higher counts of Tfr and Tfh2 cells, with a dominance of Tfh2 over Tfh1 subsets compared to other conditions. Notably, morphological irregularities (in quantity, size, and structure) of ATLOs in IgG4‐AAAs and escalated Tfr cell numbers directly correlated with IgG4‐related disease activity. All T-cell subsets were notably more concentrated within ATLOs than in areas outside these structures. Specifically, increased Tfr cells in IgG4-AAA were linked with ATLO formation. Enhanced Tfh17 cells were evident in Takayasu arteritis, while atherosclerotic and IgG4‐related inflammatory AAAs showed heightened Tfh1 cells.

This study underscores the importance of considering the imbalance in T-cell subsets in vascular lesion classification, particularly positioning IgG4‐AAA as adventitial vasculitis primarily characterized by Tfr and Tfh2 cell dominance, coupled with ATLOs’ aberrant appearance. These findings highlight the distinct immune landscape within ATLOs and the specific T-cell subset involvement in various vascular conditions, shedding light on the intricate pathophysiology underlying IgG4-related vascular diseases.

Source: ahajournals.org/doi/10.1161/JAHA.123.030356