2026-08-29T14:17:37Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/258482025-12-18T13:01:36Zcom_20.500.12105_19586com_20.500.12105_2202col_20.500.12105_19587

00925njm 22002777a 4500 dc Gómez-Morón, Álvaro author Tsukalov, Ilya author Scagnetti, Camila author Pertusa, Clara author Lozano-Prieto, Marta author Martínez-Fleta, Pedro author Requena, Silvia author Martín, Pilar author Alfranca, Aranzazu author Martin-Gayo, Enrique author Martin-Cofreces, Noa B author 2024 CD8 cytotoxic T lymphocytes (CTLs) are highly effective in defending against viral infections and tumours. They are activated through the recognition of peptide-MHC-I complex by the T-cell receptor (TCR) and co-stimulation. This cognate interaction promotes the organisation of intimate cell-cell connections that involve cytoskeleton rearrangement to enable effector function and clearance of the target cell. This is key for the asymmetric transport and mobilisation of lytic granules to the cell-cell contact, promoting directed secretion of lytic mediators such as granzymes and perforin. Mitochondria play a role in regulating CTL function by controlling processes such as calcium flux, providing the necessary energy through oxidative phosphorylation, and its own protein translation on 70S ribosomes. However, the effect of acute inhibition of cytosolic translation in the rapid response after TCR has not been studied in mature CTLs. Here, we investigated the importance of cytosolic protein synthesis in human CTLs after early TCR activation and CD28 co-stimulation for the dynamic reorganisation of the cytoskeleton, mitochondria, and lytic granules through short-term chemical inhibition of 80S ribosomes by cycloheximide and 80S and 70S by puromycin. We observed that eukaryotic ribosome function is required to allow proper asymmetric reorganisation of the tubulin cytoskeleton and mitochondria and mTOR pathway activation early upon TCR activation in human primary CTLs. Cytosolic protein translation is required to increase glucose metabolism and degranulation capacity upon TCR activation and thus to regulate the full effector function of human CTLs. Front Immunol. 2024 Jul 24:15:1411957. Frontiers in Immunology 39114656 https://hdl.handle.net/20.500.12105/25848 T cell activation cell asymmetry cytoskeleton cytotoxic CD8+ T lymphocytes immunological synapse metabolism mitochondria protein translation Cytosolic protein translation regulates cell asymmetry and function in early TCR activation of human CD8 T lymphocytes.