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However, a Th1 cytokine environment, especially the presence of gamma interferon (IFN-\u03b3), is essential for the development of primary CD8<jats:sup>+<\/jats:sup>T-cell immunity against this obligate intracellular pathogen. Earlier studies from our laboratory have demonstrated that mice lacking optimal IFN-\u03b3 levels fail to develop robust CD8<jats:sup>+<\/jats:sup>T-cell immunity against<jats:italic>T. gondii<\/jats:italic>. In the present study, induction of primary CD8<jats:sup>+<\/jats:sup>T-cell immune response against<jats:italic>T. gondii<\/jats:italic>infection was evaluated in mice infected earlier with<jats:italic>Heligmosomoides polygyrus<\/jats:italic>, a gastrointestinal worm known to evoke a polarized Th2 response in the host. In the early stage of<jats:italic>T. gondii<\/jats:italic>infection, both CD4 and CD8<jats:sup>+<\/jats:sup>T-cell responses against the parasite were suppressed in the dually infected mice. At the later stages, however,<jats:italic>T. gondii<\/jats:italic>-specific CD4<jats:sup>+<\/jats:sup>T-cell immunity recovered, while CD8<jats:sup>+<\/jats:sup>T-cell responses remained low. Unlike in mice infected with<jats:italic>T. gondii<\/jats:italic>alone, depletion of CD4<jats:sup>+<\/jats:sup>T cells in the dually infected mice led to reactivation of chronic infection, leading to<jats:italic>Toxoplasma<\/jats:italic>-related encephalitis. Our observations strongly suggest that prior infection with a Th2 cytokine-polarizing pathogen can inhibit the development of CD8<jats:sup>+<\/jats:sup>T-cell immune response against<jats:italic>T. gondii<\/jats:italic>, thus compromising long-term protection against a protozoan parasite. This is the first study to examine the generation of CD8<jats:sup>+<\/jats:sup>T-cell immune response in a parasitic nematode and protozoan coinfection model that has important implications for infections where a CD8<jats:sup>+<\/jats:sup>T-cell response is critical for host protection and reduced infection pathology.<\/jats:p>","DOI":"10.1128\/iai.01236-07","type":"journal-article","created":{"date-parts":[[2008,1,15]],"date-time":"2008-01-15T01:34:16Z","timestamp":1200360856000},"page":"1305-1313","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":38,"title":["Coinfection with<i>Heligmosomoides polygyrus<\/i>Fails To Establish CD8<sup>+<\/sup>T-Cell Immunity against<i>Toxoplasma gondii<\/i>"],"prefix":"10.1128","volume":"76","author":[{"given":"Imtiaz A.","family":"Khan","sequence":"first","affiliation":[{"name":"Department of Microbiology and Tropical Medicine and Immunology, George Washington University, Washington, DC 20037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rubeena","family":"Hakak","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Parasitology, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Eberle","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Parasitology, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Sayles","sequence":"additional","affiliation":[{"name":"Trudeau Institute, Saranac Lake, New York 12983"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis M.","family":"Weiss","sequence":"additional","affiliation":[{"name":"Department of Medicine and Pathology, Albert Einstein College of Medicine, Bronx, New York 10461"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Joseph F.","family":"Urban","sequence":"additional","affiliation":[{"name":"USDA\/ARS\/Beltsville Human Nutrition Research Center, Diet, Genomics, and Immunology Laboratory, Beltsville, Maryland 20705"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.169.6.3284"},{"key":"e_1_3_2_3_2","doi-asserted-by":"crossref","first-page":"3438","DOI":"10.4049\/jimmunol.145.10.3438","volume":"145","year":"1990","unstructured":"Brown, C. 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