{"doi":"10.1101/2023.07.27.550871","title":"TGF-β broadly modifies rather than specifically suppresses reactivated memory CD8 T cells in a dose-dependent manner","abstract":"Summary Transforming growth factor β (TGF-β) directly acts on naïve, effector and memory T cells to control cell fate decisions, which was shown using genetic abrogation of TGF-β signaling. TGF-β availability is altered by infections and cancer, however the dose-dependent effects of TGF-β on memory CD8 T cell (T mem ) reactivation are still poorly defined. We examined how activation and TGF-β signals interact to shape the functional outcome of T mem reactivation. We found that TGF-β could suppress cytotoxicity in a manner that was inversely proportional to the strength of the activating TCR or pro-inflammatory signals. In contrast, even high doses of TGF-β had a comparatively modest effect on IFN-γ expression in the context of weak and strong reactivation signals. Since CD8 T mem may not always receive TGF-β signals concurrently with reactivation, we also explored whether the temporal order of reactivation versus TGF-β signals is of importance. We found that exposure to TGF-β prior to as well as after an activation event were both sufficient to reduce cytotoxic effector function. Concurrent ATAC-seq and RNA-seq analysis revealed that TGF-β altered ∼10% of the regulatory elements induced by reactivation and also elicited transcriptional changes indicative of broadly modulated functional properties. We confirmed some changes on the protein level and found that TGF-β-induced expression of CCR8 was inversely proportional to the strength of the reactivating TCR signal. Together, our data suggest that TGF-β is not simply suppressing CD8 T mem , but modifies functional and chemotactic properties in context of their reactivation signals and in a dose-dependent manner.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":400258,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9636,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":820459,"name":"A Konecny","orcid":"0000-0002-3492-1006","position":1,"is_corresponding":false},{"id":300979,"name":"James Scott‐Browne","orcid":"0000-0002-0546-7799","position":2,"is_corresponding":false},{"id":272541,"name":"Martin Prlic","orcid":"0000-0002-0685-9321","position":3,"is_corresponding":false},{"id":655546,"name":"Alexis K Taber","orcid":"0000-0002-7012-3001","position":0,"is_corresponding":true}],"reference_count":60,"raw_metadata":null,"created_at":"2026-07-19T01:20:00.023537Z","pmid":"37546887","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}