{"doi":"10.1101/2021.06.30.450486","title":"TAILORED DC INDUCE PROTECTIVE HIV-1 SPECIFIC POLYFUNCTIONAL CD8+ T CELLS IN THE LYMPHOID TISSUE FROM HUMANIZED BLT MICE","abstract":"Abstract Effective function of CD8 + T cells and enhanced innate activation of dendritic cells (DC) in response to HIV-1 is linked to protective antiviral immunity in controllers. Manipulation of DC targeting the master regulator TANK-binding Kinase 1 (TBK1) might be useful to acquire controller-like properties. Here, we evaluated the impact of TBK1-primed DC inducing protective CD8 + T cell responses in lymphoid tissue and peripheral blood and their association with reduced HIV-1 disease progression in vivo in the humanized bone marrow, liver and thymus (hBLT) mouse model. A higher proportion of hBLT-mice vaccinated with TBK1-primed DC exhibited less severe CD4 + T cell depletion following HIV-1 infection compared to control groups. This was associated with infiltration of CD8 + T cells in the white pulp from the spleen, reduced spread of infected p24 + cells to secondary lymphoid organs and with preserved abilities of CD8 + T cells from the spleen and blood of vaccinated animals to induce specific polyfunctional responses upon antigen stimulation. Therefore, TBK1-primed DC might be an useful tool for subsequent vaccine studies. Author summary Emulating protective immunological characteristics from individuals capable of spontaneously controlling HIV-1 infection might be useful for the development of a protective vaccine. Enhanced function of dendritic cells (DC) in these HIV-1 controllers depends on the activation of TANK-binding Kinase 1 (TBK1) and might associate with protective T cells. Our study evaluated the ability of DCs trained through TBK1 activation inducing protective adaptive immune responses against HIV-1 and reducing disease progression in vivo , using a humanized mouse model. Our data indicate that mice vaccinated with tailored DC exhibit delayed disease progression, increased induction of protective CD8+ T lymphocyte subsets in the lymphoid tissue and blood upon antigen recognition. Therefore, trained-DC might be an useful tool for future HIV-1 vaccine designs.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":221132,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9548,"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":321609,"name":"Daniel T. Claiborne","orcid":"0000-0002-2091-1456","position":1,"is_corresponding":false},{"id":711851,"name":"Maud Déruaz","orcid":"0000-0001-9294-070X","position":2,"is_corresponding":false},{"id":747137,"name":"Serah Tanno","orcid":"0000-0002-7278-1075","position":3,"is_corresponding":false},{"id":747138,"name":"Carla Serra","orcid":"0000-0001-5555-0745","position":4,"is_corresponding":false},{"id":474400,"name":"Cristina Delgado‐Arévalo","orcid":null,"position":5,"is_corresponding":false},{"id":244375,"name":"Ildefonso Sánchez‐Cerrillo","orcid":"0000-0001-7262-1234","position":6,"is_corresponding":false},{"id":244382,"name":"Ignacio de los Santos","orcid":"0000-0001-7073-5211","position":7,"is_corresponding":false},{"id":747139,"name":"Jesús Sanz","orcid":"0000-0001-8740-0063","position":8,"is_corresponding":false},{"id":747140,"name":"Lucio García‐Fraile","orcid":"0000-0002-2512-6107","position":9,"is_corresponding":false},{"id":244391,"name":"Francisco Sánchez‐Madrid","orcid":"0000-0001-5303-0762","position":10,"is_corresponding":false},{"id":244390,"name":"Arántzazu Alfranca","orcid":"0000-0002-3732-5816","position":11,"is_corresponding":false},{"id":441508,"name":"María Ángeles Muñoz‐Fernández","orcid":"0000-0002-0813-4500","position":12,"is_corresponding":false},{"id":517920,"name":"Todd M. Allen","orcid":"0000-0002-6609-1318","position":13,"is_corresponding":false},{"id":263029,"name":"María J. Buzón","orcid":"0000-0003-4427-9413","position":14,"is_corresponding":false},{"id":108262,"name":"Alejandro B. Balazs","orcid":"0000-0002-1767-3944","position":15,"is_corresponding":false},{"id":330850,"name":"Vladimir Vrbanac","orcid":"0000-0002-0593-1723","position":16,"is_corresponding":false},{"id":244393,"name":"Enrique Martín‐Gayo","orcid":"0000-0002-2619-6086","position":17,"is_corresponding":false},{"id":747136,"name":"Marta Calvet‐Mirabent","orcid":"0000-0002-9134-0849","position":0,"is_corresponding":true}],"reference_count":56,"raw_metadata":null,"created_at":"2026-07-18T23:53:50.838581Z","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":[]}