{"doi":"10.1101/2021.03.13.21253527","title":"PD-1 <sup>high</sup> CXCR5 <sup>–</sup> CD4 <sup>+</sup> Peripheral Helper T (Tph) cells Promote Tissue-Homing Plasmablasts in COVID-19","abstract":"Summary A dysregulated immune response against coronavirus-2 (SARS-CoV-2) plays a critical role in the outcome of patients with coronavirus disease 2019 (COVID-19). A significant increase in circulating plasmablasts is characteristic of COVID-19 though the underlying mechanisms and its prognostic implications are not known. Here, we demonstrate that in the acute phase of COVID-19, activated PD-1 high CXCR5 − CD4 + T cells, peripheral helper T cells, (Tph) are significantly increased and promote inflammatory tissue-homing plasmablasts in patients with stable but not severe COVID-19. Analysis of scRNA-seq data revealed that plasmablasts in stable patients express higher levels of tissue-homing receptors including CXCR3 . The increased Tph cells exhibited “B cell help” signatures similar to that of circulating T follicular helper (cTfh) cells and promoted B cell differentiation in vitro . Compared with cTfh cells, Tph cells produced more IFNγ, inducing tissue-homing chemokine receptors on plasmablasts. Finally, expansion of activated Tph cells was correlated with the frequency of CXCR3 + plasmablasts in the acute phase of patients with stable disease. Our results demonstrate a novel role for Tph cells in acute viral immunity by inducing ectopic, antibody secreting plasmablasts.","journal":"medRxiv","year":2021,"id":215822,"datarank":0.368198586848484,"base_score":1.791759469228055,"endowment":1.791759469228055,"self_citation_contribution":0.26876392038420827,"citation_network_contribution":0.09943466646427573,"self_endowment_contribution":0.26876392038420827,"citer_contribution":0.09943466646427573,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":5,"citers_with_citation_signal":4,"citers_with_endowment":4,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9544,"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":105802,"name":"Subhasis Mohanty","orcid":"0000-0002-3870-2468","position":1,"is_corresponding":false},{"id":555953,"name":"Michela Comi","orcid":"0000-0002-0109-4868","position":2,"is_corresponding":false},{"id":673515,"name":"William Ruff","orcid":"0000-0001-5828-6425","position":3,"is_corresponding":false},{"id":255166,"name":"Kenneth B. 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Montgomery","orcid":"0000-0002-8661-4454","position":13,"is_corresponding":false},{"id":105840,"name":"Akiko Iwasaki","orcid":"0000-0002-7824-9856","position":14,"is_corresponding":false},{"id":105837,"name":"Charles S. Dela Cruz","orcid":"0000-0002-5258-1797","position":15,"is_corresponding":false},{"id":12162,"name":"Naftali Kaminski","orcid":"0000-0001-5917-4601","position":16,"is_corresponding":false},{"id":105833,"name":"Albert C. Shaw","orcid":"0000-0003-4970-7640","position":17,"is_corresponding":false},{"id":37332,"name":"David A. Hafler","orcid":"0000-0003-4664-535X","position":18,"is_corresponding":false},{"id":49152,"name":"Tomokazu S. 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