{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T01:29:34Z","timestamp":1787621374865,"version":"build-2736575974"},"reference-count":33,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2016,2,19]],"date-time":"2016-02-19T00:00:00Z","timestamp":1455840000000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science, and Technology","doi-asserted-by":"publisher","award":["25293101"],"award-info":[{"award-number":["25293101"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microbiology and Immunology"],"published-print":{"date-parts":[[2016,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:label\/><jats:p>CD4<jats:sup>+<\/jats:sup> T cells play critical roles in protection against the blood stage of malarial infection; however, their uncontrolled activation can be harmful to the host. In this study, in which rodent models of <jats:italic>Plasmodium<\/jats:italic> parasites were used, the expression of inhibitory receptors on activated CD4<jats:sup>+<\/jats:sup> T cells and their cytokine production was compared with their expression in a bacterial and another protozoan infection. CD4<jats:sup>+<\/jats:sup> T cells from mice infected with <jats:italic>P. yoelii<\/jats:italic> 17XL, <jats:italic>P yoelii<\/jats:italic> 17XNL, <jats:italic>P. chabaudi<\/jats:italic>, <jats:italic>P. vinckei<\/jats:italic> and <jats:italic>P. berghei<\/jats:italic> expressed the inhibitory receptors, PD\u20101 and LAG\u20103, as early as 6 days after infection, whereas those from either <jats:italic>Listeria monocytogenes\u2010<\/jats:italic> or <jats:italic>Leishmania major<\/jats:italic>\u2010infected mice did not. In response to T\u2010cell receptor stimulation, CD4<jats:sup>+<\/jats:sup> T cells from mice infected with all the pathogens under study produced high concentrations of IFN\u2010\u03b3. IL\u20102 production was reduced in mice infected with <jats:italic>Plasmodium<\/jats:italic> species, but not in those infected with <jats:italic>Listeria<\/jats:italic> or <jats:italic>Leishmania<\/jats:italic>. <jats:italic>In vitro<\/jats:italic> blockade of the interaction between PD\u20101 and its ligands resulted in increased IFN\u2010\u03b3 production in response to <jats:italic>Plasmodium<\/jats:italic> antigens, implying that PD\u20101 expressed on activated CD4<jats:sup>+<\/jats:sup> T cells actively inhibits T cell immune responses. Studies using <jats:italic>Myd88<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>, <jats:italic>Trif<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> and <jats:italic>Irf3<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice showed that induction of these CD4<jats:sup>+<\/jats:sup> T cells and their ability to produce cytokines is largely independent of TLR signaling. These studies suggest that expression of the inhibitory receptors PD\u20101 and LAG\u20103 on CD4<jats:sup>+<\/jats:sup> T cells and their reduced IL\u20102 production are common characteristic features of <jats:italic>Plasmodium<\/jats:italic> infection.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1348-0421.12354","type":"journal-article","created":{"date-parts":[[2015,12,23]],"date-time":"2015-12-23T11:16:54Z","timestamp":1450869414000},"page":"121-131","source":"Crossref","is-referenced-by-count":25,"title":["Expression of PD\u20101\/LAG\u20103 and cytokine production by CD4<sup>+<\/sup> T cells during infection with <i>Plasmodium<\/i> parasites"],"prefix":"10.1111","volume":"60","author":[{"given":"Henrietta T.","family":"Doe","sequence":"first","affiliation":[{"name":"Division of Immunology Department of Molecular Microbiology and Immunology Graduate School of Biomedical Sciences Nagasaki University 1\u201012\u20104 Sakamoto Nagasaki 852\u20108523 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Kimura","sequence":"additional","affiliation":[{"name":"Division of Immunology Department of Molecular Microbiology and Immunology Graduate School of Biomedical Sciences Nagasaki University 1\u201012\u20104 Sakamoto Nagasaki 852\u20108523 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mana","family":"Miyakoda","sequence":"additional","affiliation":[{"name":"Division of Immunology Department of Molecular Microbiology and Immunology Graduate School of Biomedical Sciences Nagasaki University 1\u201012\u20104 Sakamoto Nagasaki 852\u20108523 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazumi","family":"Kimura","sequence":"additional","affiliation":[{"name":"Division of Immunology Department of Molecular Microbiology and Immunology Graduate School of Biomedical Sciences Nagasaki University 1\u201012\u20104 Sakamoto Nagasaki 852\u20108523 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masoud","family":"Akbari","sequence":"additional","affiliation":[{"name":"Division of Immunology Department of Molecular Microbiology and Immunology Graduate School of Biomedical Sciences Nagasaki University 1\u201012\u20104 Sakamoto Nagasaki 852\u20108523 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuyuki","family":"Yui","sequence":"additional","affiliation":[{"name":"Division of Immunology Department of Molecular Microbiology and Immunology Graduate School of Biomedical Sciences Nagasaki University 1\u201012\u20104 Sakamoto Nagasaki 852\u20108523 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,2,19]]},"reference":[{"key":"e_1_2_8_2_1","unstructured":"WHO.World Malaria Report2015. 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