{"doi":"10.7554/elife.70989","title":"Sepsis leads to lasting changes in phenotype and function of memory CD8 T cells","abstract":"The global health burden due to sepsis and the associated cytokine storm is substantial. While early intervention has improved survival during the cytokine storm, those that survive can enter a state of chronic immunoparalysis defined by transient lymphopenia and functional deficits of surviving cells. Memory CD8 T cells provide rapid cytolysis and cytokine production following re-encounter with their cognate antigen to promote long-term immunity, and CD8 T cell impairment due to sepsis can pre-dispose individuals to re-infection. While the acute influence of sepsis on memory CD8 T cells has been characterized, if and to what extent pre-existing memory CD8 T cells recover remains unknown. Here, we observed that central memory CD8 T cells (T CM ) from septic patients proliferate more than those from healthy individuals. Utilizing LCMV immune mice and a CLP model to induce sepsis, we demonstrated that T CM proliferation is associated with numerical recovery of pathogen-specific memory CD8 T cells following sepsis-induced lymphopenia. This increased proliferation leads to changes in composition of memory CD8 T cell compartment and altered tissue localization. Further, memory CD8 T cells from sepsis survivors have an altered transcriptional profile and chromatin accessibility indicating long-lasting T cell intrinsic changes. The sepsis-induced changes in the composition of the memory CD8 T cell pool and transcriptional landscape culminated in altered T cell function and reduced capacity to control L. monocytogenes infection. Thus, sepsis leads to long-term alterations in memory CD8 T cell phenotype, protective function and localization potentially changing host capacity to respond to re-infection.","journal":"eLife","year":2021,"id":164338,"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":39,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9462,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":373436,"name":"Xiang Li","orcid":"0000-0002-8931-3681","position":1,"is_corresponding":false},{"id":447062,"name":"Patrick W. McGonagill","orcid":"0000-0001-8308-127X","position":2,"is_corresponding":false},{"id":286407,"name":"Qiang Shan","orcid":"0000-0002-7089-0278","position":3,"is_corresponding":false},{"id":685366,"name":"Micaela G. Fosdick","orcid":"0000-0002-2427-532X","position":4,"is_corresponding":false},{"id":521130,"name":"Mikaela M. Tremblay","orcid":"0000-0001-9952-5381","position":5,"is_corresponding":false},{"id":521131,"name":"Jon C. D. Houtman","orcid":"0000-0002-5307-9854","position":6,"is_corresponding":false},{"id":271042,"name":"Hai‐Hui Xue","orcid":"0000-0002-9163-7669","position":7,"is_corresponding":false},{"id":250879,"name":"Thomas S. Griffith","orcid":"0000-0002-7205-9859","position":8,"is_corresponding":false},{"id":317054,"name":"Weiqun Peng","orcid":"0000-0001-5521-9091","position":9,"is_corresponding":false},{"id":250878,"name":"Vladimir P. Badovinac","orcid":"0000-0003-3180-2439","position":10,"is_corresponding":false},{"id":447061,"name":"Isaac J. Jensen","orcid":"0000-0002-3107-3961","position":0,"is_corresponding":true}],"reference_count":87,"raw_metadata":null,"created_at":"2026-07-18T23:45:27.031465Z","pmid":"34652273","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":[]}