{"doi":"10.3389/fmicb.2021.763030","title":"Cell-Extrinsic Priming Increases Permissiveness of CD4+ T Cells to Human Immunodeficiency Virus Infection by Increasing C–C Chemokine Receptor Type 5 Co-receptor Expression and Cellular Activation Status","abstract":"The chemokine receptor CCR5 is expressed on multiple cell types, including macrophages, dendritic cells, and T cells, and is the major co-receptor used during HIV transmission. Using a standard αCD3/CD28 in vitro stimulation protocol to render CD4+ T cells from PBMCs permissive to HIV infection, we discovered that the percentage of CCR5 + T cells was significantly elevated in CD4+ T cells when stimulated in the presence of peripheral blood mononuclear cells (PBMCs) as compared to when stimulated as purified CD4+ T cells. This indicated that environmental factors unique to the T-PBMCs condition affect surface expression of CCR5 on CD4+ T cells. Conditioned media from αCD3/CD28-stimulated PBMCs induced CCR5 expression in cultures of unstimulated cells. Cytokine profile analysis of these media suggests IL-12 as an inducer of CCR5 expression. Mass cytometric analysis showed that stimulated T-PBMCs exhibited a uniquely activated phenotype compared to T-Pure. In line with increased CCR5 expression and activation status in stimulated T-PBMCs, CD4+ T cells from these cultures were more susceptible to infection by CCR5-tropic HIV-1 as compared with T-Pure cells. These results suggest that in order to increase ex vivo infection rates of blood-derived CD4+ T cells, standard stimulation protocols used in HIV infection studies should implement T-PBMCs or purified CD4+ T cells should be supplemented with IL-12.","journal":"Frontiers in Microbiology","year":2021,"id":205583,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"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":0.9564,"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":760633,"name":"Johanne H. Egedal","orcid":"0000-0002-1102-2323","position":1,"is_corresponding":false},{"id":707967,"name":"Thomas Packard","orcid":"0000-0003-4807-9101","position":2,"is_corresponding":false},{"id":789348,"name":"Karthiga Thavachelvam","orcid":null,"position":3,"is_corresponding":false},{"id":246059,"name":"Guorui Xie","orcid":"0000-0002-9295-2724","position":4,"is_corresponding":false},{"id":350092,"name":"Renée M. van der Sluis","orcid":"0000-0002-7668-2517","position":5,"is_corresponding":false},{"id":28871,"name":"Warner C. Greene","orcid":"0000-0001-9896-8615","position":6,"is_corresponding":false},{"id":71692,"name":"Nadia R. Roan","orcid":"0000-0002-5464-1976","position":7,"is_corresponding":false},{"id":350103,"name":"Martin R. Jakobsen","orcid":"0000-0001-8847-9201","position":8,"is_corresponding":false},{"id":789347,"name":"Jesper G. Pedersen","orcid":null,"position":0,"is_corresponding":true}],"reference_count":53,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:51:33.996102Z","pmid":"34899645","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":[]}