PT  - JOURNAL ARTICLE
AU  - Kojo, Satoshi
AU  - Ohno-Oishi, Michiko
AU  - Wada, Hisashi
AU  - Nieke, Sebastian
AU  - Seo, Wooseok
AU  - Muroi, Sawako
AU  - Taniuchi, Ichiro
TI  - Constitutive CD8 expression drives innate CD8<sup>+</sup> T-cell differentiation via induction of iNKT2 cells
AID  - 10.26508/lsa.202000642
DP  - 2020 Feb 01
TA  - Life Science Alliance
PG  - e202000642
VI  - 3
IP  - 2
4099  - http://www.life-science-alliance.org/content/3/2/e202000642.short
4100  - http://www.life-science-alliance.org/content/3/2/e202000642.full
SO  - Life Sci. Alliance2020 Feb 01; 3
AB  - 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.