{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T16:50:20Z","timestamp":1781110220631,"version":"3.54.1"},"reference-count":44,"publisher":"National Academy of Sciences","issue":"28","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2005,7,12]]},"abstract":"<jats:p>\n                    Inducible costimulator (ICOS) has been suggested to perform an important role in T helper cell type 2 (Th2) responses, germinal center formation, and isotype switching. The role of ICOS in chronic Th2 responses was studied in a nematode model with the filarial parasite,\n                    <jats:italic>Brugia malayi<\/jats:italic>\n                    . Contrary to expectations, we did not observe a significant defect in IL-4-producing Th2 cells in ICOS\u2013\/\u2013 mice or in eosinophil recruitment. We also found that ICOS was not required for the differentiation of alternatively activated macrophages (AAM\u03a6) that express Ym1 and Fizz1. Although the production of IgE was slightly reduced in ICOS\u2013\/\u2013 mice, this was not as significant as in CD28\u2013\/\u2013 mice. In contrast to live infection, the primary response of ICOS\u2013\/\u2013 mice immunized with soluble\n                    <jats:italic>B. malayi<\/jats:italic>\n                    antigen and complete Freund's adjuvant resulted in significantly fewer IL-4-producing cells in the lymph nodes. As previously reported, we observed a defect in antibody isotype switching toward the IgG1 isotype in ICOS\u2013\/\u2013 mice during live infection. Interestingly, there was a significant enhancement of parasite-specific IgG3 isotype antibodies. CD28\u2013\/\u2013 and MHC class II\u2013\/\u2013 mice also had enhanced parasite-specific IgG3 isotype antibodies. Our results suggest that ICOS is not required to maintain a chronic cellular Th2 response. The primary role of ICOS in a chronic helminth infection could be to drive antibodies toward type 2 isotypes. T-independent antibody response to the parasite could be enhanced in the absence of costimulation and T cell help.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0503961102","type":"journal-article","created":{"date-parts":[[2005,7,1]],"date-time":"2005-07-01T20:49:41Z","timestamp":1120250981000},"page":"9872-9877","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":16,"title":["Inducible costimulator is required for type 2 antibody isotype switching but not T helper cell type 2 responses in chronic nematode infection"],"prefix":"10.1073","volume":"102","author":[{"given":"P'ng","family":"Loke","sequence":"first","affiliation":[{"name":"Departments of Pathology and Medicine and Microbiology\/Immunology, University of California, San Francisco, CA 94143; Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, Immunology Program, New York, NY 10021; University of California, Davis, CA 95616; and Institute of Cell, Animal, and Population Biology, University of Edinburgh, Edinburgh EH9 3JT, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingxing","family":"Zang","sequence":"additional","affiliation":[{"name":"Departments of Pathology and Medicine and Microbiology\/Immunology, University of California, San Francisco, CA 94143; Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, Immunology Program, New York, NY 10021; University of California, Davis, CA 95616; and Institute of Cell, Animal, and Population Biology, University of Edinburgh, Edinburgh EH9 3JT, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Hsuan","sequence":"additional","affiliation":[{"name":"Departments of Pathology and Medicine and Microbiology\/Immunology, University of California, San Francisco, CA 94143; Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, Immunology Program, New York, NY 10021; University of California, Davis, CA 95616; and Institute of Cell, Animal, and Population Biology, University of Edinburgh, Edinburgh EH9 3JT, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Waitz","sequence":"additional","affiliation":[{"name":"Departments of Pathology and Medicine and Microbiology\/Immunology, University of California, San Francisco, CA 94143; Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, Immunology Program, New York, NY 10021; University of California, Davis, CA 95616; and Institute of Cell, Animal, and Population Biology, University of Edinburgh, Edinburgh EH9 3JT, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard M.","family":"Locksley","sequence":"additional","affiliation":[{"name":"Departments of Pathology and Medicine and Microbiology\/Immunology, University of California, San Francisco, CA 94143; Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, Immunology Program, New York, NY 10021; University of California, Davis, CA 95616; and Institute of Cell, Animal, and Population Biology, University of Edinburgh, Edinburgh EH9 3JT, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith E.","family":"Allen","sequence":"additional","affiliation":[{"name":"Departments of Pathology and Medicine and Microbiology\/Immunology, University of California, San Francisco, CA 94143; Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, Immunology Program, New York, NY 10021; University of California, Davis, CA 95616; and Institute of Cell, Animal, and Population Biology, University of Edinburgh, Edinburgh EH9 3JT, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James P.","family":"Allison","sequence":"additional","affiliation":[{"name":"Departments of Pathology and Medicine and Microbiology\/Immunology, University of California, San Francisco, CA 94143; Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, Immunology Program, New York, NY 10021; University of California, Davis, CA 95616; and Institute of Cell, Animal, and Population Biology, University of Edinburgh, Edinburgh EH9 3JT, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2005,7]]},"reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.20.091101.091806"},{"key":"e_1_3_2_2_2","first-page":"515","volume":"23","year":"2004","unstructured":"Greenwald, R. 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