{"doi":"10.3389/fimmu.2020.590568","title":"PD-1 Blockade Reverses Obesity-Mediated T Cell Priming Impairment","abstract":"Despite obesity reaching pandemic proportions, its impact on antigen-specific T cell responses is still unclear. We have recently demonstrated that obesity results in increased expression of PD-1 on T cells, and checkpoint blockade targeting PD-1/PD-L1 surprisingly resulted in greater clinical efficacy in cancer therapy. Adverse events associated with this therapy center around autoimmune reactions. In this study, we examined the impact of obesity on T cell priming and on autoimmune pathogenesis using the mouse model experimental autoimmune encephalomyelitis (EAE), which is mediated by autoreactive myelin-specific T cells generated after immunization. We observed that diet-induced obese (DIO) mice had a markedly delayed EAE onset and developed milder clinical symptoms compared to mice on control diet (CD). This delay was associated with impaired generation of myelin-specific T cell numbers and concurrently correlated with increased PD-L1 upregulation on antigen-presenting cells in secondary lymphoid organs. PD-1 blockade during the priming stage of EAE restored disease onset and severity and increased numbers of pathogenic CD4+ T cells in the central nervous system (CNS) of DIO mice to similar levels to those of CD mice. Administration of anti-PD-1 after onset of clinical symptoms did not increase EAE pathogenesis demonstrating that initial priming is the critical juncture affected by obesity. These findings demonstrate that obesity impairs antigen-specific T cell priming, but this can be reversed with PD-1 blockade. Our results further suggest that PD-1 blockade may increase the risk of autoimmune toxicities, particularly in obesity.","journal":"Frontiers in Immunology","year":2020,"id":70728,"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":19,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9562,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":262404,"name":"Lam T. Khuat","orcid":"0000-0002-4223-8805","position":1,"is_corresponding":false},{"id":374122,"name":"Sofia Caryotakis","orcid":"0000-0003-3522-0022","position":2,"is_corresponding":false},{"id":374123,"name":"Marilyn Wang","orcid":"0000-0001-6500-3809","position":3,"is_corresponding":false},{"id":262401,"name":"Cordelia Dunai","orcid":"0000-0001-5799-2387","position":4,"is_corresponding":false},{"id":374124,"name":"Alan V. Nguyen","orcid":"0000-0002-2249-7244","position":5,"is_corresponding":false},{"id":288709,"name":"Logan V. Vick","orcid":"0009-0006-9778-0120","position":6,"is_corresponding":false},{"id":262405,"name":"Kevin Stoffel","orcid":"0000-0003-1428-7471","position":7,"is_corresponding":false},{"id":52067,"name":"Bruce R. Blazar","orcid":"0000-0002-9608-9841","position":8,"is_corresponding":false},{"id":259311,"name":"Arta M. Monjazeb","orcid":"0000-0001-5175-8004","position":9,"is_corresponding":false},{"id":259312,"name":"William J. Murphy","orcid":"0000-0002-2793-401X","position":10,"is_corresponding":false},{"id":374125,"name":"Athena M. Soulika","orcid":"0000-0001-6746-3876","position":11,"is_corresponding":false},{"id":323876,"name":"Catherine T. Le","orcid":"0000-0002-0175-570X","position":0,"is_corresponding":true}],"reference_count":78,"raw_metadata":null,"created_at":"2026-07-18T21:43:32.585486Z","pmid":"33193426","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":[]}