{"doi":"10.1093/jimmun/vkaf283.421","title":"Aging compromises effector differentiation and induces exhaustion-like phenotype in CD8 T cells 2511","abstract":"Abstract Description Immunosenescence leads to impaired immunity against infections in the elderly. As a key component of adaptive immunity, T cells are crucial for immunity against infection and cancer and exhibit distinct phenotypic changes with age. Characterizing these age-related alterations in T cells is essential for developing strategies to address immune dysregulation in the elderly. In vitro activation model showed that aged mice have a higher frequency of PD1+ exhausted-like CD8 T cells at baseline and higher TCR-induced cell death upon activation. Inhibiting both apoptosis and necrosis rescues TCR activation-induced cell death. Using a murine hepatitis virus (MHV) intranasal infection model, we observed that aged mice had greater weight loss, higher mortality, and impaired CD8 T cell responses during MHV infection. Infected aged mice exhibited increased expression of inhibitory receptors on antiviral CD8 T cells and a decrease in the population of CD8 T cells producing IFN-γ. Single-cell RNA sequencing showed that aging altered the transcriptional profile of antiviral CD8 T cells and reduced T-Bet and ZEB2 expression, key factors for effector CD8 T cell differentiation. Aging also upregulated T cell exhaustion gene signature mediated by the transcription factor TOX. Overall, our findings demonstrate that aging reshapes the molecular program of antiviral CD8 T cells and compromised antiviral T cell immunity in the aged. Funding Sources Supported by NIH/ NIA AG-083398; NIAID AI-158294 Topic Categories Viral Immunology (VIR)","journal":"The Journal of Immunology","year":2025,"id":582239,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9574,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":623483,"name":"Tuoqi Wu","orcid":"0000-0002-4003-1034","position":1,"is_corresponding":false},{"id":1494017,"name":"Yao Chen","orcid":"0000-0002-2336-3432","position":2,"is_corresponding":false},{"id":484320,"name":"Ziang Zhu","orcid":"0009-0008-4231-7213","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T02:58:55.657290Z","pmid":null,"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":[]}