{"doi":"10.1073/pnas.1108945108","title":"Direct activation of antigen-presenting cells is required for CD8\n                    <sup>+</sup>\n                    T-cell priming and tumor vaccination","abstract":"<jats:p>\n                    Successful priming of adaptive immune responses is crucially dependent on innate activation signals that convert resting antigen-presenting cells (APCs) into immunogenic ones. APCs expressing the relevant innate pattern recognition receptors can be directly activated by pathogen-associated molecular patterns (PAMPs) to become competent to prime T-cell responses. Alternatively, it has been suggested that APCs could be activated indirectly by proinflammatory mediators synthesized by PAMP-exposed cells. However, data obtained with CD4\n                    <jats:sup>+</jats:sup>\n                    T cells suggest that inflammatory signals often cannot substitute for direct pattern recognition in APC activation for the priming of T helper responses. To test whether the same is true for CD8\n                    <jats:sup>+</jats:sup>\n                    T cells, we studied cytotoxic T lymphocyte development in vitro and in mixed chimeric mice in which coexisting APCs can either present a preprocessed model antigen or directly recognize a given PAMP, but not both. We show that indirectly activated APCs promote antigen-specific proliferation of naïve CD8\n                    <jats:sup>+</jats:sup>\n                    T cells but fail to support their survival and cytotoxic T lymphocyte differentiation. Furthermore, CD8\n                    <jats:sup>+</jats:sup>\n                    T cells primed by indirectly activated APCs are unable to reject tumors. Thus, inflammation cannot substitute for direct recognition of single PAMPs in CD8\n                    <jats:sup>+</jats:sup>\n                    T-cell priming. These findings have important practical implications for vaccine design, indicating that adjuvants must be judiciously chosen to trigger the relevant pattern recognition receptors in APCs.\n                  </jats:p>","journal":"Proceedings of the National Academy of Sciences","year":2011,"id":597495,"datarank":0.6862066467755076,"base_score":4.574710978503383,"endowment":4.574710978503383,"self_citation_contribution":0.6862066467755076,"citation_network_contribution":0.0,"self_endowment_contribution":0.6862066467755076,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":96,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1199824,"name":"Caetano Reis e Sousa","orcid":"0000-0001-7392-2119","position":1,"is_corresponding":false},{"id":557489,"name":"Annette Oxenius","orcid":"0000-0002-2079-2354","position":2,"is_corresponding":false},{"id":1530755,"name":"Roman Spörri","orcid":null,"position":3,"is_corresponding":false},{"id":1530754,"name":"Wolfgang Kratky","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Direct activation of antigen-presenting cells is required for CD8\n                    <sup>+</sup>\n                    T-cell priming and tumor vaccination","abstract":"<jats:p>\n                    Successful priming of adaptive immune responses is crucially dependent on innate activation signals that convert resting antigen-presenting cells (APCs) into immunogenic ones. APCs expressing the relevant innate pattern recognition receptors can be directly activated by pathogen-associated molecular patterns (PAMPs) to become competent to prime T-cell responses. Alternatively, it has been suggested that APCs could be activated indirectly by proinflammatory mediators synthesized by PAMP-exposed cells. However, data obtained with CD4\n                    <jats:sup>+</jats:sup>\n                    T cells suggest that inflammatory signals often cannot substitute for direct pattern recognition in APC activation for the priming of T helper responses. To test whether the same is true for CD8\n                    <jats:sup>+</jats:sup>\n                    T cells, we studied cytotoxic T lymphocyte development in vitro and in mixed chimeric mice in which coexisting APCs can either present a preprocessed model antigen or directly recognize a given PAMP, but not both. We show that indirectly activated APCs promote antigen-specific proliferation of naïve CD8\n                    <jats:sup>+</jats:sup>\n                    T cells but fail to support their survival and cytotoxic T lymphocyte differentiation. Furthermore, CD8\n                    <jats:sup>+</jats:sup>\n                    T cells primed by indirectly activated APCs are unable to reject tumors. Thus, inflammation cannot substitute for direct recognition of single PAMPs in CD8\n                    <jats:sup>+</jats:sup>\n                    T-cell priming. These findings have important practical implications for vaccine design, indicating that adjuvants must be judiciously chosen to trigger the relevant pattern recognition receptors in APCs.\n                  </jats:p>","is_dataset_classified":null,"base_score":4.574710978503383,"endowment":4.574710978503383,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"21987815","pmcid":"PMC3198339","openalex_id":"https://openalex.org/W2115019081","authors":[],"funders":[{"funder_name":"Cancer Research UK","grant_id":"","title":null}],"total_grants":1,"fwci":2.9674,"citation_percentile":0.91642104,"influential_citations":0,"citation_trend":[{"year":2012,"count":10},{"year":2013,"count":10},{"year":2014,"count":6},{"year":2015,"count":10},{"year":2016,"count":4},{"year":2017,"count":8},{"year":2018,"count":4},{"year":2019,"count":2},{"year":2020,"count":7},{"year":2021,"count":6},{"year":2022,"count":5},{"year":2023,"count":8},{"year":2024,"count":8},{"year":2025,"count":6},{"year":2026,"count":2}],"oa_status":"closed","license":null,"oa_locations":[{"url":"https://pnas.org/doi/pdf/10.1073/pnas.1108945108","host_type":"publisher"},{"url":"https://doi.org/10.1073/pnas.1108945108","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/21987815","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3198339","host_type":"repository"}],"fields_of_study":["Immunotherapy and Immune Responses","T-cell and B-cell Immunology","Immune Cell Function and Interaction"],"mesh_terms":["Animals","Antigen-Presenting Cells","Cell Differentiation","Cell Survival","Female","Immunity, Innate","Male","Melanoma, Experimental","Mice, Inbred C57BL","Radiation Chimera","T-Lymphocytes, Cytotoxic","Mice, Knockout","CD8-Positive T-Lymphocytes","Cancer Vaccines","Cell Proliferation","Mice","Adaptive Immunity"],"keywords":["Priming (agriculture)","Cytotoxic T cell","Antigen-presenting cell","Immunology","T cell","Antigen","Biology","CD8","Acquired immune system","Cell biology","Immune system","In vitro","Biochemistry"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-28T13:25:55.387845Z","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":[]}