Aligned with the previous theory regarding tonic TCR signalling, increased tonic TCR signals observed in anti-CD19/22 CAR T-cell therapy led to upregulation of inhibitory receptor genes, such as lymphocyte-activation gene (LAG) and cytotoxic T-lymphocyte-associated protein 4 (CTLA4), and downregulation of memory-related genes (lymphoid enhancer-binding factor 1 [LEF1], T-cell factor 7 [TCF7], interleukin 7 receptor [IL7R], and Kruppel-like factor 2 [KLF2]), which might explain the lesser occurrence of severe CRS in this CAR T-cell type [56]. This evidence concerns the gene CD19 and congenital rubella syndrome.