T1D samples showed reduced PRDM1 and core suppressive markers, such as ENTPD1/CD39, LAG3, NRP1, TBX21, but increased activation markers, including CD44, CD69, ICOS, CXCR3, pro-inflammatory Th17-associated transcripts, such as GATA3, IL17B, IL23R, RORA and TCR signaling genes, including LCK, NR4A1/Nur77, ZAP70, with concurrent IL6 downregulation, aligning with the TCR hyperactivation model we proposed. Here, TBX21 is linked to type 1 diabetes mellitus.