TNF and CD107a-dominated enhanced effector responses of CD8+ MAIT cells to Escherichia coli stimulation in patients with aplastic anemia.

BACKGROUND: Mucosal-associated invariant T (MAIT) cells are innate-like T cells that respond rapidly to microbial metabolites presented by MR1. Patients with aplastic anemia (AA) are prone to bacterial and fungal infections, but the MR1-related effector responses of MAIT cells in AA remain unclear. METHODS: Peripheral blood mononuclear cells from 27 patients with AA and 29 healthy individuals were stimulated with fixed Escherichia coli for 2, 3, 6, or 12 h, with or without MR1 blockade. CD8+ MAIT cell activation, cytokine production, degranulation, CD69 expression, and polyfunctional profiles were assessed by flow cytometry. RESULTS: CD8+ MAIT cells from patients with AA showed higher CD69 expression under unstimulated conditions, suggesting a basal activation state. After fixed E. coli stimulation, CD8+ MAIT cells from patients with AA displayed enhanced early effector responses compared with those from healthy individuals, characterized by increased TNF production, CD107a expression, and polyfunctional subset frequencies, particularly CD107a+TNF+ populations. These enhanced responses were most pronounced at 6 h after stimulation. MR1 blockade markedly reduced E. coli-induced cytokine production and CD107a expression in CD8+ MAIT cells, supporting an important contribution of MR1-dependent signaling to these responses. CONCLUSIONS: In patients with AA, CD8+ MAIT cells display markedly enhanced effector functions and polyfunctional responses upon E. coli stimulation. These findings indicate that riboflavin metabolism-related bacterial infection in patients with AA can induce functional disorders of CD8+ MAIT cells via the MR1-TCR pathway.