{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T21:17:01Z","timestamp":1790371021697,"version":"4.1.0"},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2009,12,14]],"date-time":"2009-12-14T00:00:00Z","timestamp":1260748800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R01HL092797"],"award-info":[{"award-number":["1R01HL092797"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The T cell\u2013mediated immune response elicited by Pneumocystis plays a key role in pulmonary damage and dysfunction during Pneumocystis carinii pneumonia (PcP). Mice depleted of CD4+ and CD8+ T cells prior to infection are markedly protected from PcP-related respiratory deficit and death, despite progressive lung infection. However, the therapeutic effectiveness of Ab-mediated disruption of T cell function in mice already displaying clinical symptoms of disease has not been determined. Therefore, a murine model of PcP-related immune reconstitution inflammatory syndrome was used to assess whether Ab to the pan-T cell molecule CD3 is effective for reducing the severity of PcP when administered after the onset of disease. Mice that received anti-CD3 Ab exhibited a rapid and dramatic halt in the PcP-associated pulmonary function decline within 1 week after treatment, and a striking enhancement of survival rate compared with mice receiving the control Ab. Physiologic improvement in anti-CD3 treated mice was associated with a significant reduction in the number of CD4+ and CD8+ T cells recovered in lung lavage fluid. This effectiveness of anti-CD3 was noted whether the mice also received antibiotic therapy with trimethoprim-sulfamethoxazole. These data suggest that monoclonal Ab-mediated disruption of T cell function may represent a specific and effective adjunctive therapy to rapidly reverse the ongoing pathologic immune response occurring during active PcP. Thus, the anti-human CD3 monoclonal Ab OKT3, which is already in clinical use, has the potential to be developed as an adjunctive therapy for PcP.<\/jats:p>","DOI":"10.4049\/jimmunol.0901864","type":"journal-article","created":{"date-parts":[[2009,12,1]],"date-time":"2009-12-01T03:38:26Z","timestamp":1259638706000},"page":"497-502","source":"Crossref","is-referenced-by-count":22,"title":["Anti-CD3 Antibody Decreases Inflammation and Improves Outcome in a Murine Model of <i>Pneumocystis<\/i> Pneumonia"],"prefix":"10.1093","volume":"184","author":[{"given":"Samir P","family":"Bhagwat","sequence":"first","affiliation":[{"name":"Department of Pediatrics , Rochester, NY 14642"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terry W","family":"Wright","sequence":"additional","affiliation":[{"name":"Department of Pediatrics , Rochester, NY 14642"},{"name":"Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry , Rochester, NY 14642"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis","family":"Gigliotti","sequence":"additional","affiliation":[{"name":"Department of Pediatrics , Rochester, NY 14642"},{"name":"Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry , Rochester, NY 14642"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,12,14]]},"reference":[{"key":"2025032710014597400_r1","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1055\/s-2008-1063852","article-title":"Pneumocystis pneumonia.","volume":"29","author":"D\u2019Avignon","year":"2008","journal-title":"Semin. 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Immunol."},{"key":"2025032710014597400_r11","first-page":"1058","article-title":"Prognostic value of interleukin-8 in AIDS-associated Pneumocystis carinii pneumonia.","volume":"151","author":"Benfield","year":"1995","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"2025032710014597400_r12","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1164\/ajrccm\/140.5.1204","article-title":"Pneumocystis carinii pneumonia. Differences in lung parasite number and inflammation in patients with and without AIDS.","volume":"140","author":"Limper","year":"1989","journal-title":"Am. Rev. Respir. Dis."},{"key":"2025032710014597400_r13","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1053\/srin.2001.22731","article-title":"Anti-inflammatory treatment of acute and chronic pneumonia.","volume":"16","author":"Skerrett","year":"2001","journal-title":"Semin. Respir. 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