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We compared the roles of CD28- and CD40 ligand (CD40L)-mediated costimulation in<jats:italic>C. muridarum<\/jats:italic>infection. Mice with CD28 or CD80\/CD86 gene knockout (KO) displayed an infection course similar to that of wild-type mice during both primary and secondary infection, suggesting that CD28-mediated costimulation is not required for protection against<jats:italic>C. muridarum<\/jats:italic>infection. However, mice deficient in CD40L or CD40 displayed a prolonged infection course after primary or secondary infection, suggesting that CD40-CD40L costimulation plays an essential role in the development of anti-<jats:italic>C. muridarum<\/jats:italic>immunity. Interestingly, the CD28- or CD80\/CD86-deficient mice displayed significantly lower levels of inflammatory pathologies in the upper genital tracts after primary infection, although the attenuation in inflammation was no longer significant during secondary infection. However, the CD40L or CD40 KO mice developed inflammatory pathologies as severe as those in wild-type mice following either primary or secondary infection despite the obvious deficits in adaptive immunity in these KO mice. The resistance of CD28 or CD80\/CD86 KO mice to chlamydial infection correlated with production of gamma interferon, while the development of inflammatory pathologies in CD40L or CD40 KO mice correlated with the production of other proinflammatory cytokines in mouse urogenital tracts during the early stages of the infection. These observations together suggest that<jats:italic>C. muridarum<\/jats:italic>-induced protective immunity and inflammatory pathologies can be mediated by distinct costimulatory signals.<\/jats:p>","DOI":"10.1128\/iai.00611-08","type":"journal-article","created":{"date-parts":[[2009,4,28]],"date-time":"2009-04-28T01:23:00Z","timestamp":1240881780000},"page":"3080-3089","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":30,"title":["Distinct Roles of CD28- and CD40 Ligand-Mediated Costimulation in the Development of Protective Immunity and Pathology during<i>Chlamydia muridarum<\/i>Urogenital Infection in Mice"],"prefix":"10.1128","volume":"77","author":[{"given":"Lili","family":"Chen","sequence":"first","affiliation":[{"name":"Departments of Microbiology and Immunology"},{"name":"Department of Pathogen Biology, University of South China, 28 Changshen Rd., Hengyang"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen","family":"Cheng","sequence":"additional","affiliation":[{"name":"Departments of Microbiology and Immunology"},{"name":"Department of Immunology, Xiangya Medical School, The Central South University, 168 Tongzipo Rd., Changsha, Hunan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pooja","family":"Shivshankar","sequence":"additional","affiliation":[{"name":"Departments of Microbiology and Immunology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Lei","sequence":"additional","affiliation":[{"name":"Departments of Microbiology and Immunology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Departments of Microbiology and Immunology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yimou","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pathogen Biology, University of South China, 28 Changshen Rd., Hengyang"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I-Tien","family":"Yeh","sequence":"additional","affiliation":[{"name":"Pathology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, Texas 78229"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guangming","family":"Zhong","sequence":"additional","affiliation":[{"name":"Departments of Microbiology and Immunology"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","first-page":"401","volume":"5","year":"1993","unstructured":"Armitage, R. 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