{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T21:17:02Z","timestamp":1790371022330,"version":"4.1.0"},"reference-count":70,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2013,1,1]],"date-time":"2013-01-01T00:00:00Z","timestamp":1356998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Little is known about the role of NK cells or their interplay with other immune cells during opportunistic infections. Using our murine model of Pneumocystis pneumonia, we found that loss of NK cells during immunosuppression results in substantial Pneumocystis lung burden. During early infection of C57B\/6 CD4+ T cell\u2013depleted mice, there were significantly fewer NK cells in the lung tissue compared with CD4+ T cell\u2013intact animals, and the NK cells present demonstrated decreased upregulation of the activation marker NKp46 and production of the effector cytokine, IFN-\u03b3. Furthermore, coincubation studies revealed a significant increase in fungal killing when NK cells were combined with CD4+ T cells compared with either cell alone, which was coincident with a significant increase in perforin production by NK cells. Finally, however, we found through adoptive transfer that memory CD4+ T cells are required for significant NK cell upregulation of the activation marker NK group 2D and production of IFN-\u03b3, granzyme B, and perforin during Pneumocystis infection. To the best of our knowledge, this study is the first to demonstrate a role for NK cells in immunity to Pneumocystis pneumonia, as well as to establish a functional relationship between CD4+ T cells and NK cells in the host response to an opportunistic fungal pathogen.<\/jats:p>","DOI":"10.4049\/jimmunol.1200861","type":"journal-article","created":{"date-parts":[[2012,12,2]],"date-time":"2012-12-02T01:35:45Z","timestamp":1354412145000},"page":"285-295","source":"Crossref","is-referenced-by-count":55,"title":["Memory CD4+ T Cells Are Required for Optimal NK Cell Effector Functions against the Opportunistic Fungal Pathogen <i>Pneumocystis murina<\/i>"],"prefix":"10.1093","volume":"190","author":[{"given":"Michelle N","family":"Kelly","sequence":"first","affiliation":[{"name":"Section of Pulmonary and Critical Care Medicine, Department of Medicine, School of Medicine, Louisiana State University Health Sciences Center , New Orleans, LA 70112"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingquan","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Children\u2019s Hospital of Pittsburgh of University of Pittsburgh Medical Center, University of Pittsburgh School of Medicine , Pittsburgh, PA 15213"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanbao","family":"Ruan","sequence":"additional","affiliation":[{"name":"Section of Pulmonary and Critical Care Medicine, Department of Medicine, School of Medicine, Louisiana State University Health Sciences Center , New Orleans, LA 70112"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay","family":"Kolls","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Children\u2019s Hospital of Pittsburgh of University of Pittsburgh Medical Center, University of Pittsburgh School of Medicine , Pittsburgh, PA 15213"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain","family":"D\u2019Souza","sequence":"additional","affiliation":[{"name":"Section of Pulmonary and Critical Care Medicine, Department of Medicine, School of Medicine, Louisiana State University Health Sciences Center , New Orleans, LA 70112"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judd E","family":"Shellito","sequence":"additional","affiliation":[{"name":"Section of Pulmonary and Critical Care Medicine, Department of Medicine, School of Medicine, Louisiana State University Health Sciences Center , New Orleans, LA 70112"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,1,1]]},"reference":[{"key":"2025032406210754700_r1","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1038\/ni1582","article-title":"Functions of natural killer cells","volume":"9","author":"Vivier","year":"2008","journal-title":"Nat. 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