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Cytokine receptor & gamma;c effectuates the generation of proinflammatory innate CD8 T cells by non-classical MHC-I molecules
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- Authors
- Issue Date
- 2023-07
- Publisher
- Academic Press
- Citation
- Journal of Autoimmunity, Vol.138, p. 103059
- Abstract
- Innate CD8 T cells correspond to a population of terminally differentiated effector T cells that phenotypically appear as antigen-experienced memory cells and functionally resemble proinflammatory CD8 T cells, expressing copious amounts of IFN?. Innate CD8 T cells, however, are distinct from conventional effector-memory CD8 T cells as they acquire functional maturity during their generation in the thymus. Understanding the molecular mechanisms that drive their thymic development and differentiation is an intensely studied subject in T cell immunity, and here we identified the cytokine receptor ?c as a critical mediator of innate CD8 T cell generation that promotes their selection even in the absence of classical MHC-I molecules. Consequently, overexpression of ?c resulted in a dramatic increase of innate CD8 T cells in (KDb)-D-b-deficient mice. We mapped its underlying mechanism to the expansion of IL-4-producing invariant NKT cells, so that it is the increased availability of intrathymic IL-4 which augments the selection of innate CD8 T cells. Collectively, these results unravel the selection of innate CD8 T cells being mediated by non-classical MHC-I molecules and being modulated by the abundance of the ?c cytokine, IL-4.
- ISSN
- 0896-8411
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