Gene expression of Tfh cells in the lessions of IgG4-related disease.

To address a possible role of Tfh (CD3+CD4+CXCR5hiPD-1hi) cells in IgG4-related disease(IgG4-RD), we investigated Tfh cells as well as other lymphocyte subsets residing within the affected tissue lesions of IgG4-RD in this study. When compared to gene expression profiles of Tfh cells within tonsils, inflammatory lesions in IgG4-RD preferentially contained Tfh cells with the expression of signature genes of cytotoxic T lymphocytes. Whereas the expression levels of Tfh-related genes like IL-21, CD200, and Pou2af1 (also named as Bob1) in GC-type Tfh cells of IgG4-RD seemed to be relatively lower than those of GC-type Tfh cells within tonsils. GC-type Tfh cells of IgG4-RD expressed low levels of genes related to Th2 cells, Th17 cells, and Treg cells, albeit the genes related to Th1 cells and interaction of T cells and B cells. T follicular helper (Tfh) cells shape humoral immunity by helping B cell responses at initial and recall phases. Recent studies indicate a possible involvement of Tfh cells in the process of chronic inflammation; however, the functional role of Tfh cells in persistent immune settings still unclear. Here we report a unique capacity of CD4+CD8+ (double positive, DP: CD3+CD4+CD8+PD-1hiCXCR5hi) Tfh cells, which abundantly resided in the fibroinflammatory lesions of IgG4-related disease (IgG4-RD). According to transcriptome analyses, DP-Tfh cells in the lesions of IgG4-RD preferentially expressed the signature genes identifying cytotoxic CD8+ T cells. These findings may illustrate a potential feedback loop for immune tolerance operated by such Tfh cell species in chronic inflammatory conditions.