{"doi":"10.1371/journal.ppat.1011720","title":"Sepsis leads to lasting changes in phenotype and function of naïve CD8 T cells","abstract":"Sepsis, an amplified immune response to systemic infection, is characterized by a transient cytokine storm followed by chronic immune dysfunction. Consequently, sepsis survivors are highly susceptible to newly introduced infections, suggesting sepsis can influence the function and composition of the naïve CD8 T cell pool and resulting pathogen-induced primary CD8 T cell responses. Here, we explored the extent to which sepsis induces phenotypic and functional changes within the naïve CD8 T cell pool. To interrogate this, the cecal ligation and puncture (CLP) mouse model of polymicrobial sepsis was used. In normal, non-septic mice, we show type-I interferon (IFN I)-mediated signaling plays an important role in driving the phenotypic and functional heterogeneity in the naïve CD8 T cell compartment leading to increased representation of Ly6C+ naïve CD8 T cells. In response to viral infection after sepsis resolution, naïve Ly6C+ CD8 T cells generated more primary effector and memory CD8 T cells with slower conversion to a central memory CD8 T cell phenotype (Tcm) than Ly6C- naïve CD8 T cells. Importantly, as a potent inducer of cytokine storm and IFN I production, sepsis leads to increased representation of Ly6C+ naïve CD8 T cells that maintained their heightened ability to respond (i.e., effector and memory CD8 T cell accumulation and cytokine production) to primary LCMV infection. Lastly, longitudinal analyses of peripheral blood samples obtained from septic patients revealed profound changes in CD8 T cell subset composition and frequency compared to healthy controls. Thus, sepsis has the capacity to alter the composition of naïve CD8 T cells, directly influencing primary CD8 T cell responses to newly introduced infections.","journal":"PLoS Pathogens","year":2023,"id":337684,"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":18,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.946,"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":1070108,"name":"Patrick W. McGonagil","orcid":null,"position":1,"is_corresponding":false},{"id":447061,"name":"Isaac J. Jensen","orcid":"0000-0002-3107-3961","position":2,"is_corresponding":false},{"id":352237,"name":"Tiffany K. Ybarra","orcid":null,"position":3,"is_corresponding":false},{"id":372345,"name":"Gail A. Bishop","orcid":"0000-0002-1291-5078","position":4,"is_corresponding":false},{"id":397894,"name":"John T. Harty","orcid":"0000-0001-7266-2802","position":5,"is_corresponding":false},{"id":250879,"name":"Thomas S. Griffith","orcid":"0000-0002-7205-9859","position":6,"is_corresponding":false},{"id":250878,"name":"Vladimir P. Badovinac","orcid":"0000-0003-3180-2439","position":7,"is_corresponding":false},{"id":1069554,"name":"Roger R. Berton","orcid":"0000-0003-1517-8541","position":0,"is_corresponding":true}],"reference_count":65,"raw_metadata":null,"created_at":"2026-07-19T01:10:31.133446Z","pmid":"37824591","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":[]}