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The present study examines whether mice that lack expression of CD28 as a result of gene targeting are capable of generating a Th2 response characteristic during infection with the intravascular trematode parasite <jats:italic>Schistosoma mansoni<\/jats:italic>. Mutant and control mice were either inoculated in the footpad with <jats:italic>S. mansoni<\/jats:italic> eggs (a potent inducer of a Th2 response) or infected percutaneously with the parasite. Draining lymph nodes (after footpad injection) or spleen cells (after natural infection) were harvested at 12 days and 8 weeks, respectively, and examined for cytokine responses to egg antigens. CD28\u2010deficient mice (\u2212\/\u2212) generated diminished egg antigen\u2010driven interleukin (IL)\u20104 and IL\u20105 production (by 5\u2010 to 17\u2010fold, respectively) compared to CD28\u2010expressing (+\/+) littermates. In contrast, lymphocyte proliferation and interferon (IFN)\u2010\u03b3 production to egg antigens were equivalent for mutant and control mice. Infected CD28\u2212\/\u2212 mice also had reduced immunoglobulin secretion. Serum levels of parasite antigen\u2010specific IgG1 and polyclonal IgE were significantly diminished in CD28\u2212\/\u2212 compared to CD28+\/+ mice. Lack of CD28 expression had no effect on granuloma formation around eggs trapped in the liver, but increased susceptibility of mice to primary schistosomiasis infection. These studies indicate that CD28 activation contributes to T cell priming required for generation of a Th2 response to an intravascular dwelling helminth parasite.<\/jats:p>","DOI":"10.1002\/eji.1830261027","type":"journal-article","created":{"date-parts":[[2007,3,2]],"date-time":"2007-03-02T01:33:12Z","timestamp":1172799192000},"page":"2448-2455","source":"Crossref","is-referenced-by-count":49,"title":["CD28\u2010deficient mice generate an impaired Th2 response to <i>Schistosoma mansoni<\/i> infection"],"prefix":"10.1002","volume":"26","author":[{"given":"Christopher L.","family":"King","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia","family":"Xianli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carl H.","family":"June","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryo","family":"Abe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kelvin P.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,11,23]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0167-5699(94)90080-9"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7694361"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(05)80001-7"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.177.3.845"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.182.2.459"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.270.5238.932"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.270.5238.985"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1496399"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1323143"},{"key":"e_1_2_1_11_2","doi-asserted-by":"crossref","first-page":"4142","DOI":"10.4049\/jimmunol.153.9.4142","volume":"153","author":"Corry D. 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