Tcf7 and Lef1 also restrain expression of cytotoxicity genes in naïve CD8 cells (55), so their downregulation, together with Stat1 GOF, could contribute to the up-regulation of a Type I/cytotoxicity program marked by expression of Tbx21, Gzmk, Nkg7, Cst7, Cxcr3 and Cxcl10. Tcf7 and Lef1 also critically regulate Tfh differentiation and Bcl6 induction during infection-induced Tfh differentiation (33, 35), so their Stat1T385M-induced down-regulation could contribute to the lack of Bcl6 expression by mutant Tfh-like CD4 cells. The gene discussed is GZMK; the disease is infection.