Tox2 is required for the maintenance of GC TFH cells and the generation of memory TFH cells

Memory T follicular helper (T-FH) cells play an essential role to induce secondary antibody response by providing help to memory and naive B cells. Here, we show that the transcription factor Tox2 is vital for the maintenance of T-FH cells in germinal centers (GCs) and the generation of memory T-FH cells. High Tox2 expression was almost exclusive to GC T-FH cells among human tonsillar and blood CD4(+) T cell subsets. Tox2 overexpression maintained the expression of T-FH-associated genes in T cell receptor-stimulated human GC T-FH cells and inhibited their spontaneous conversion into T(H)1-like cells. Tox2-deficient mice displayed impaired secondary T-FH cell expansion upon reimmunization with an antigen and upon secondary infection with a heterologous influenza virus. Collectively, our study shows that Tox2 is highly integrated into establishment of durable GC T-FH cell responses and development of memory T-FH cells in mice and humans.

Automated summary

Tox2 plays a vital role in maintaining T-FH cells and generating memory T-FH cells, while its overexpression can inhibit the spontaneous conversion of T-FH cells into T(H)1-like cells. Tox2 deficiency leads to impaired expansion of secondary T-FH cells upon reimmunization and secondary infection.