Tox2 is required for the maintenance of GC T<sub>FH</sub> cells and the generation of memory T<sub>FH</sub> cells.

Horiuchi, Shu; Wu, Hanchih; Liu, Wen-Chun; Schmitt, Nathalie; Provot, Jonathan; Liu, Yang; Bentebibel, Salah-Eddine; Albrecht, Randy A et al. · Sci Adv · 2021

basic_science · Level V

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Abstract

Memory T follicular helper (T<sub>FH</sub>) 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<sub>FH</sub> cells in germinal centers (GCs) and the generation of memory T<sub>FH</sub> cells. High Tox2 expression was almost exclusive to GC T<sub>FH</sub> cells among human tonsillar and blood CD4<sup>+</sup> T cell subsets. Tox2 overexpression maintained the expression of T<sub>FH</sub>-associated genes in T cell receptor–stimulated human GC T<sub>FH</sub> cells and inhibited their spontaneous conversion into T<sub>H</sub>1-like cells. Tox2-deficient mice displayed impaired secondary T<sub>FH</sub> 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<sub>FH</sub> cell responses and development of memory T<sub>FH</sub> cells in mice and humans.