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

The histone methyltransferase NSD2 controls CD8+ T cell differentiation and fate during acute viral infection through the H3K36me2-Zbtb20 axis. NSD2 loss enhances early expansion of activated CD8+ T cells but severely impairs survival fitness during the contraction phase, causing disproportionate collapse of the antigen-specific pool and limiting long-term memory formation. In tumors, NSD2 loss also raises the proportion of resident memory T cells, which show a dysfunctional phenotype.