Fig. P1.

Model depicts the development of conventional vs. innate CD8⁺ T cells in the thymus. The strength of TCR signaling regulates Eomesodermin expression via the Tec family tyrosine kinase ITK and the transcription factor IRF4. Strong TCR signaling promotes robust activation of ITK, leading to high levels of expression of the transcription factor IRF4. Either in the presence or the absence of IL-4, CD8⁺ T cells stimulated under these conditions express low levels of Eomesodermin (Eomes). During T-cell development in the thymus, this pathway produces conventional T cells. In contrast, following weak TCR stimulation, ITK activation is modest and cells produce low amounts of IRF4.These conditions, together with IL-4 receptor signaling, promote maximal up-regulation of Eomesodermin, leading to the development of innate CD8⁺ T cells.