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Publication : Constitutive CD8 expression drives innate CD8<sup>+</sup> T-cell differentiation via induction of iNKT2 cells.

First Author  Kojo S Year  2020
Journal  Life Sci Alliance Volume  3
Issue  2 PubMed ID  31980555
Mgi Jnum  J:287231 Mgi Id  MGI:6391629
Doi  10.26508/lsa.202000642 Citation  Kojo S, et al. (2020) Constitutive CD8 expression drives innate CD8(+) T-cell differentiation via induction of iNKT2 cells. Life Sci Alliance 3(2)
abstractText  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 CD8alpha 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.
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