Gene expression of CD4+CD8+ Tfh cells in lesions of IgG4-related disease and CD4+CD8+ Tfh in tonsil.

To further know features of CD4+CD8+ Double positive (DP)-Tfh cells in respective lymphoid tissues, we subsequently investigated transcriptomes of DP-Tfh cells in submandibular gland lesions of IgG4-RD in comparison to those of DP-Tfh cells in tonsils. Results showed that DP-Tfh cells of IgG4-RD lesions were more apt to present CTL-related genes such as Eomes and granzymes than DP-Tfh cells in tonsils. It was also noted that the level of CD70 in DP-Tfh cells of IgG4-RD lesions was higher than that of tonsillar DP-Tfh cells. Genes related to Tfh cell function were seemed to be presented in DP-Tfh cells of tonsils compared to DP-Tfh cells of IgG4-RD lesions. 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.