Complement receptor CD46 co-stimulates optimal human CD8⁺ T cell effector function via fatty acid metabolism.

ABSTRACT: The induction of human CD4⁺ Th1 cells requires autocrine stimulation of the complement receptor CD46 in direct crosstalk with a CD4⁺ T cell-intrinsic NLRP3 inflammasome. However, it is unclear whether human cytotoxic CD8⁺ T cell (CTL) responses also rely on an intrinsic complement-inflammasome axis. Here we show, using CTLs from patients with CD46 deficiency or with constitutively-active NLRP3, that CD46 delivers co-stimulatory signals for optimal CTL activity by augmenting nutrient-influx and fatty acid synthesis. Surprisingly, although CTLs express NLRP3, a canonical NLRP3 inflammasome is not required for normal human CTL activity, as CTLs from patients with hyperactive NLRP3 activity function normally. These findings establish autocrine complement and CD

SUBMITTER: Arbore G 

PROVIDER: S-EPMC6180132 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature