Histone methyltransferase NSD2 shapes CD8+ T cell fates through the H3K36me2-Zbtb20 axis

During this process, CD8+ T cells exhibit substantial plasticity in their differentiation trajectory. Notably, epigenetic regulation has emerged as a pivotal mechanism to govern T cell fate decisions.

In this study, we demonstrate that the histone methyltransferase NSD2 critically regulates CD8+ T cell differentiation during acute viral infection. While NSD2 deficiency enhances the early expansion of activated CD8+ T cells, it severely compromises their survival fitness during the contraction phase, leading to a disproportionate collapse of the antigen-specific pool and limiting the establishment of robust long-lived memory.