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The following is a summary of “Single-cell transcriptomics reveals granzyme K–expressing cytotoxic Tfh cells in tertiary lymphoid structures in IgG4-RD,” published in the February 2024 issue of Allergy & Immunology by Aoyagi, et al.
Germinal center (GC) responses orchestrated by T follicular helper (Tfh) and T follicular regulatory (Tfr) cells are pivotal for generating high-affinity antibodies. The induction of acquired immune responses to tissue-released antigens often occurs in tertiary lymphoid organs (TLOs), particularly those containing GCs in affected tissues. IgG4-related disease (IgG4-RD) is characterized by polarized isotype switching and the presence of TLOs in affected tissues. In this study, we utilized single-cell transcriptomics of tissue-infiltrating T cells from these TLOs to gain an unbiased understanding of tissue-infiltrating GC-Tfh cells. For a study, researchers sought to identify subsets of GC-Tfh cells in TLOs of patients with IgG4-RD using single-cell transcriptomics.
Single-cell RNA sequencing of sorted CD3+ T cells and multicolor immunofluorescence analysis were employed to investigate CD4+CXCR5+Bcl6+ GC-Tfh cells in affected lesions from patients diagnosed with IgG4-RD.
Infiltrating CD4+CXCR5+Bcl6+ Tfh cells were categorized into five main clusters. Notably, they identified HLA+ granzyme K+ (GZMK+) Tfh cells exhibiting cytotoxicity-associated features in patients with IgG4-RD. Additionally, they observed a significant presence of infiltrating Tfr cells displaying suppressor-associated features in IgG4-RD patients. These GZMK+ Tfh cells and Tfr cells were found to cluster together within affected tissues from individuals with IgG4-RD.
The single-cell dataset unveiled a novel subset of HLA+GZMK+ cytotoxic Tfh cells infiltrating affected organs in patients with IgG4-RD, suggesting a potential role for infiltrating Tfr cells in suppressing cytotoxic Tfh cells.
Reference: jacionline.org/article/S0091-6749(23)01072-2/abstract