{"doi":"10.3389/fimmu.2019.03005","title":"Overexpression of CD6 and PD-1 Identifies Dysfunctional CD8+ T-Cells During Chronic SIV Infection of Rhesus Macaques","abstract":"Effective CD8 + T-cell responses play an important role in determining the course of SIV/HIV viral infection. Here we identified a unique population of dysfunctional CD8 + T-cells in lymphoid tissues and bronchoalveolar lavage (BAL) of rhesus macaques with chronic SIV infection characterized by co-expression of CD6 and PD-1. The frequency of CD6 and PD-1 co-expressing CD8 + T-cells was significantly increased in lymphoid tissues and BAL during chronic SIV infection compared to pre-infection levels. These CD6 + PD-1 + CD8 + T-cells displayed impaired proliferation, cytokine secretion and cytotoxicity compared to their CD6 -PD-1 + CD8 + T cell counterparts. The frequency of CD8 + PD-1 + and CD8 + CD6 -PD-1 + T-cells in the lymph node and bone marrow did not correlate with SIV viral load, whereas the frequency of CD8 + CD6 + PD-1 + T-cells positively correlated with SIV viral load in these tissues highlighting the contribution of CD6 to disease progression. CD6 + PD-1 + CD8 + T-cells expressed elevated levels of SHP2 phosphatase compared to CD6 -PD-1 + CD8 + T-cells providing a potential mechanism by which CD6 may induce T-cell dysfunction during chronic SIV infection. Combined targeting of CD6 and PD-1 effectively revived the CD8 + T-cell proliferative response in vitro suggesting a strategy for potential therapeutic benefit.","journal":"Frontiers in Immunology","year":2020,"id":84445,"datarank":0.533290631193673,"base_score":2.302585092994046,"endowment":2.302585092994046,"self_citation_contribution":0.3453877639491069,"citation_network_contribution":0.1879028672445661,"self_endowment_contribution":0.3453877639491069,"citer_contribution":0.1879028672445661,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":9,"citers_with_citation_signal":7,"citers_with_endowment":7,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9511,"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":331835,"name":"Anthony Nwankwo","orcid":"0000-0002-0895-8673","position":1,"is_corresponding":false},{"id":383714,"name":"Mohammad Arif Rahman","orcid":"0000-0002-6120-8943","position":2,"is_corresponding":false},{"id":383716,"name":"Ruth Hunegnaw","orcid":"0000-0002-4212-5245","position":3,"is_corresponding":false},{"id":383713,"name":"Christopher Hogge","orcid":"0000-0002-8143-3435","position":4,"is_corresponding":false},{"id":383712,"name":"Sabrina Helmold Hait","orcid":"0000-0001-8609-2310","position":5,"is_corresponding":false},{"id":383715,"name":"Eun‐Ju Ko","orcid":"0000-0002-1081-904X","position":6,"is_corresponding":false},{"id":384494,"name":"Tanya Hoang","orcid":null,"position":7,"is_corresponding":false},{"id":383719,"name":"Marjorie Robert-Guroff","orcid":"0000-0003-0606-6636","position":8,"is_corresponding":false},{"id":291523,"name":"Gospel Enyindah-Asonye","orcid":"0000-0002-4575-9622","position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T21:55:38.506333Z","pmid":"31998302","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":[]}