Tox2 is required for the maintenance of GC T(FH) cells and the generation of memory T(FH) cells

Memory T follicular helper (T(FH)) cells play an essential role to induce secondary antibody response by providing help to memory and naïve 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.