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. |