{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T09:02:13Z","timestamp":1790413333795,"version":"4.1.0"},"reference-count":34,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2011,11,1]],"date-time":"2011-11-01T00:00:00Z","timestamp":1320105600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2011,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>We have previously revealed the protective role of CD8<jats:sup>+<\/jats:sup>T cells in host defense against<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Histoplasma capsulatum<\/jats:named-content>in animals with CD4<jats:sup>+<\/jats:sup>T cell deficiency and demonstrated that sensitized CD8<jats:sup>+<\/jats:sup>T cells are restimulated<jats:italic>in vitro<\/jats:italic>by dendritic cells that have ingested apoptotic macrophage-associated<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Histoplasma<\/jats:named-content>antigen. Here we show that immunization with apoptotic phagocytes containing heat-killed<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Histoplasma<\/jats:named-content>efficiently activated functional CD8<jats:sup>+<\/jats:sup>T cells whose contribution was equal to that of CD4<jats:sup>+<\/jats:sup>T cells in protection against<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Histoplasma<\/jats:named-content>challenge. Inhibition of macrophage apoptosis due to inducible nitric oxide synthase (iNOS) deficiency or by caspase inhibitor treatment dampened the CD8<jats:sup>+<\/jats:sup>T cell but not the CD4<jats:sup>+<\/jats:sup>T cell response to pulmonary<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Histoplasma<\/jats:named-content>infection. In mice subcutaneously immunized with viable<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Histoplasma<\/jats:named-content>yeasts whose CD8<jats:sup>+<\/jats:sup>T cells are protective against<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Histoplasma<\/jats:named-content>challenge, there was heavy granulocyte and macrophage infiltration and the infiltrating cells became apoptotic. In mice subcutaneously immunized with carboxyfluorescein diacetate succinimidyl ester (CFSE)-labeled apoptotic macrophages containing heat-killed<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Histoplasma<\/jats:named-content>, the CFSE-labeled macrophage material was found to localize within dendritic cells in the draining lymph node. Moreover, depleting dendritic cells in immunized CD11c-DTR mice significantly reduced CD8<jats:sup>+<\/jats:sup>T cell activation. Taken together, our results revealed that phagocyte apoptosis in the<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Histoplasma<\/jats:named-content>-infected host is associated with CD8<jats:sup>+<\/jats:sup>T cell activation and that immunization with apoptotic phagocytes containing heat-killed<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Histoplasma<\/jats:named-content>efficiently evokes a protective CD8<jats:sup>+<\/jats:sup>T cell response. These results suggest that employing apoptotic phagocytes as antigen donor cells is a viable approach for the development of efficacious vaccines to elicit strong CD8<jats:sup>+<\/jats:sup>T cell as well as CD4<jats:sup>+<\/jats:sup>T cell responses to<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Histoplasma<\/jats:named-content>infection.<\/jats:p>","DOI":"10.1128\/iai.05350-11","type":"journal-article","created":{"date-parts":[[2011,9,13]],"date-time":"2011-09-13T06:31:35Z","timestamp":1315895495000},"page":"4493-4502","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":21,"title":["Immunization with Apoptotic Phagocytes Containing Histoplasma capsulatum Activates Functional CD8<sup>+<\/sup>T Cells To Protect against Histoplasmosis"],"prefix":"10.1128","volume":"79","author":[{"given":"Shih-Hung","family":"Hsieh","sequence":"first","affiliation":[{"name":"Graduate Institute of Immunology, National Taiwan University College of Medicine, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jr-Shiuan","family":"Lin","sequence":"additional","affiliation":[{"name":"Graduate Institute of Immunology, National Taiwan University College of Medicine, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juin-Hua","family":"Huang","sequence":"additional","affiliation":[{"name":"Graduate Institute of Immunology, National Taiwan University College of Medicine, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shang-Yang","family":"Wu","sequence":"additional","affiliation":[{"name":"Graduate Institute of Immunology, National Taiwan University College of Medicine, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ching-Liang","family":"Chu","sequence":"additional","affiliation":[{"name":"Graduate Institute of Immunology, National Taiwan University College of Medicine, Taipei, Taiwan"},{"name":"Immunology Research Center, National Health and Research Institutes, Miaoli, Taiwan"},{"name":"Yeastern Biotech Co., Taipei County, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John T.","family":"Kung","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology, Academia Sinica, Nankang, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Betty A.","family":"Wu-Hsieh","sequence":"additional","affiliation":[{"name":"Graduate Institute of Immunology, National Taiwan University College of Medicine, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/32183"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI25365"},{"key":"e_1_3_2_4_2","doi-asserted-by":"crossref","first-page":"7389","DOI":"10.4049\/jimmunol.162.12.7389","article-title":"Complex requirements for nascent and memory immunity in pulmonary histoplasmosis","volume":"162","author":"Allend\u00f6rfer R.","year":"1999","unstructured":"Allend\u00f6rferR.BrunnerG. 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