Gene expression of CD4+CD8+ Tfh cells and CD4+CD8- Tfh in tonsil.

To understand physiological characteristics of CD4+CD8+ Double-positive (DP)-Tfh cells, we continued to conduct comparative transcriptome analysis of tonsillar Tfh cell populations, including DP-Tfh cells and CD4+CD8- single-positive (SP)-Tfh cells as a control. Results showed that DP-Tfh cells preferentially expressed transcripts related to CTLs, such as CD8 (CD8A and CD8B), Eomes, and granzymes, suggesting a possible cytotoxic attribute of DP-Tfh cells. Th1-cell related signature genes were also presented in DP-Tfh cells and cytokines like interferon (IFN)-gamma and interleukin (IL)-10 were found to be highly presented in DP-Tfh cells rather than SP-Tfh cells. Of note, the expression profile of authentic Tfh-cell (i.e. SP-Tfh cell) related genes like IL-4, IL-21, Bcl6, and Pou2af1 seemed to be shared with DP-Tfh 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.