{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T18:06:38Z","timestamp":1785521198976,"version":"3.56.0"},"reference-count":65,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2025,7,19]],"date-time":"2025-07-19T00:00:00Z","timestamp":1752883200000},"content-version":"vor","delay-in-days":5,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"LMK and BSL by Midwestern Unversity"},{"name":"Master of Biomedical Sciences Program"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,7,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Dendritic cells (DCs) and natural killer (NK) cells engage in reciprocal interactions to trigger an efficient innate immune response while governing downstream adaptive immunity. Here, we used an ex vivo autologous human primary immune cell coculture system of DCs and NK cells to examine their impact on na\u00efve CD4+ and CD8+ T cell (CD3+CD45RA+CD197+) activation in response to influenza A viral (IAV) infection. Using multiparameter flow cytometry, we observed that culturing T cells with both DCs and NK cells enhanced CD69 expression on CD4+ and CD8+ T cells, increased CD25 on CD4+ T cells, and promoted CD8+ T cell proliferation, compared with cultures with only NK cells or DCs. When DCs were exposed to the pandemic A\/California\/07\/2009 (H1N1) strain or the A\/Victoria\/361\/2011 (H3N2) strain, subsequent coculture with NK cells reduced the frequency of CD4+CD69+ and CD8+CD69+ na\u00efve T cells. Notably, H3N2, but not H1N1, exposure also reduced CD4+CD25+ T cell frequencies. The IAV-mediated curtailment of T cell activation was dependent on viral replication because exposure to DCs with irradiated the H1N1 strain followed increased the frequency of CD4+CD69+, CD8+CD69+, CD4+CD25+, and CD8+CD25+ T cells, while irradiation of H3N2 increased the frequency of CD4+CD69+, CD8+CD69+ and proliferation of CD4+ and CD8+ T cells. These findings demonstrate that IAV can partially subvert DC-NK cell crosstalk to impair na\u00efve T cell activation in a strain-dependent manner. This knowledge may guide the design of next-generation influenza vaccines to elicit robust cellular immune responses.<\/jats:p>","DOI":"10.1093\/immhor\/vlaf024","type":"journal-article","created":{"date-parts":[[2025,7,19]],"date-time":"2025-07-19T06:50:09Z","timestamp":1752907809000},"source":"Crossref","is-referenced-by-count":2,"title":["Influenza A virus disruption of dendritic cell-natural killer cell crosstalk impacts activation of na\u00efve helper and cytotoxic T cell subsets"],"prefix":"10.1093","volume":"9","author":[{"given":"Connor A","family":"Morson","sequence":"first","affiliation":[{"name":"Master of Biomedical Sciences Program, Midwestern University , Glendale, AZ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3883-0427","authenticated-orcid":false,"given":"Chandana K","family":"Uppalapati","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, College of Graduate Studies, Midwestern University , Glendale, AZ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4635-9970","authenticated-orcid":false,"given":"Brina S","family":"Lopez","sequence":"additional","affiliation":[{"name":"Farm Animal Medicine, College of Veterinary Medicine, Midwestern University , Glendale, AZ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa M","family":"Kronstad","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, College of Graduate Studies, Midwestern University , Glendale, AZ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,7,18]]},"reference":[{"key":"2025071902500013400_vlaf024-B1","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/S2213-2600(18)30496-X","article-title":"Mortality, morbidity, and hospitalisations due to influenza lower respiratory tract infections, 2017: an analysis for the Global Burden of Disease Study 2017","volume":"7","author":"Troeger","year":"2019","journal-title":"Lancet Respir Med"},{"key":"2025071902500013400_vlaf024-B2","doi-asserted-by":"publisher","first-page":"1546","DOI":"10.1093\/infdis\/jiv577","article-title":"Influenza vaccine effectiveness against 2009 pandemic influenza A(H1N1) virus differed by vaccine type during 2013\u20132014 in the United States","volume":"213","author":"Gaglani","year":"2016","journal-title":"J Infect Dis"},{"key":"2025071902500013400_vlaf024-B3","doi-asserted-by":"publisher","first-page":"1529","DOI":"10.1093\/infdis\/jiu647","article-title":"Influenza vaccine effectiveness in the United States during 2012-2013: variable protection by age and virus type","volume":"211","author":"McLean","year":"2015","journal-title":"J Infect Dis"},{"key":"2025071902500013400_vlaf024-B4","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1093\/cid\/cit736","article-title":"Influenza vaccine effectiveness in the 2011\u20132012 season: protection against each circulating virus and the effect of prior vaccination on estimates","volume":"58","author":"Ohmit","year":"2014","journal-title":"Clin Infect Dis"},{"key":"2025071902500013400_vlaf024-B5","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1126\/science.aaz8432","article-title":"Influenza vaccine\u2013induced human bone marrow plasma cells decline within a year after vaccination","volume":"370","author":"Davis","year":"2020","journal-title":"Science"},{"key":"2025071902500013400_vlaf024-B6","doi-asserted-by":"crossref","first-page":"518","DOI":"10.7326\/0003-4819-123-7-199510010-00008","article-title":"The efficacy of influenza vaccine in elderly persons. 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