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

Memory T follicular helper (T) 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 cells in germinal centers (GCs) and the generation of memory T cells. High Tox2 expression was almost exclusive to GC T cells among human tonsillar and blood CD4 T cell subsets. Tox2 overexpression maintained the expression of T-associated genes in T cell receptor–stimulated human GC T cells and inhibited their spontaneous conversion into T1-like cells. Tox2-deficient mice displayed impaired secondary T 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 cell responses and development of memory T cells in mice and humans.