Figure 5. T-cell lineages in mammals and cartilaginous fishes.
a, Schematic diagram of mammalian CD8+ cytotoxic cells producing various effector molecules, such as PRF1 (perforin), GZM (granzymes), INF-γ (interferon-γ) and TNF-α (tumour necrosis factor-α). Interleukins 7 (IL-7) and 15 (IL-15) are indispensable for induction of the transcription factor RUNX3, which controls expression of the genes encoding the CD8 co-receptor that interacts with the TCR and MHC class I molecules. All key elements of this T-cell lineage are present in the genomes of cartilaginous fishes. b, Diversification of CD4 lineages in mammals. The transcription factor ThPOK controls expression of the co-receptor CD4, which interacts with the TCR and MHC class II molecules and represses the CD8 lineage programme. The listed inducer cytokines activate key transcriptional regulators that define the multiple CD4+ lineages specialized for producing various effector molecules; genes not found in cartilaginous fishes are struck through. Cartilaginous fishes probably possess only TH1 cells (red rectangle) and lack other helper subsets. TGF-β, transforming growth factor-β.