TY - JOUR T1 - Constitutive CD8 expression drives innate CD8<sup>+</sup> T-cell differentiation via induction of iNKT2 cells JF - Life Science Alliance JO - Life Sci. Alliance DO - 10.26508/lsa.202000642 VL - 3 IS - 2 SP - e202000642 AU - Satoshi Kojo AU - Michiko Ohno-Oishi AU - Hisashi Wada AU - Sebastian Nieke AU - Wooseok Seo AU - Sawako Muroi AU - Ichiro Taniuchi Y1 - 2020/02/01 UR - https://www.life-science-alliance.org/content/3/2/e202000642.abstract N2 - Temporal down-regulation of the CD8 co-receptor after receiving positive-selection signals has been proposed to serve as an important determinant to segregate helper versus cytotoxic lineages by generating differences in the duration of TCR signaling between MHC-I and MHC-II selected thymocytes. By contrast, little is known about whether CD8 also modulates TCR signaling engaged by the non-classical MHC-I–like molecule, CD1d, during development of invariant natural killer T (iNKT) cells. Here, we show that constitutive transgenic CD8 expression resulted in enhanced differentiation of innate memory-like CD8+ thymocytes in both a cell-intrinsic and cell-extrinsic manner, the latter being accomplished by an increase in the IL-4–producing iNKT2 subset. Skewed iNKT2 differentiation requires cysteine residues in the intracellular domain of CD8α that are essential for transmitting cellular signaling. Collectively, these findings shed a new light on the relevance of CD8 down-regulation in shaping the balance of iNKT-cell subsets by modulating TCR signaling. ER -