TOX2

Overview

TOX2 (Thymocyte Selection Associated HMG Box Protein 2) is an HMG-box transcription factor involved in Tfh cell differentiation. TOX2 cooperates with BCL6 and promotes the Tfh gene programme. In the context of dengue, TOX2 expression marks the IL-21⁺ helper Tph subcluster — the subset of CXCR5⁻PD-1⁺ peripheral helper T cells that is competent to provide B cell help.

Key Points from Literature

  • TOX2 marks the helper Tph subcluster: scRNA-seq of activated CD4⁺ T cells from acute dengue identified an IL-21⁺ helper Tph cluster co-expressing ICOS, MAF, and TOX2. TOX2 expression in this Tph context is notable because TOX2 is classically associated with Tfh differentiation — its expression on CXCR5⁻ cells suggests these Tph share part of the Tfh transcriptional programme while lacking follicle-homing capacity (see Ansari2025 - Peripheral T Helper Subset Drives B Cell Response in Dengue, 10x Genomics scRNA-seq, 4,361 cells, n=4 patients).

Contradictions & Debates

None documented in current wiki sources.

Peripheral Helper T Cell, HOPX, IL-21, CXCR5

Sources