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Here, we quantitatively dissected the immune and disease responses to repeated<jats:italic>Chlamydia pneumoniae<\/jats:italic>lung infection by multivariate modeling with four dichotomous effects: mouse strain (A\/J or C57BL\/6), dietary protein content (14% protein and 0.3%<jats:sc>l<\/jats:sc>-cysteine-0.9%<jats:sc>l<\/jats:sc>-arginine, or 24% protein and 0.5%<jats:sc>l<\/jats:sc>-cysteine-2.0%<jats:sc>l<\/jats:sc>-arginine), dietary antioxidant content (90 IU \u03b1-tocopherol\/kg body weight versus 450 IU \u03b1-tocopherol\/kg and 0.1% g<jats:sc>l<\/jats:sc>-ascorbate), and time course (3 or 10 days postinfection). Following intranasal<jats:italic>C. pneumoniae<\/jats:italic>challenge, C57BL\/6 mice on a low-protein\/low-antioxidant diet, but not C57BL\/6 mice on other diets or A\/J mice, exhibited profoundly suppressed early lung inflammatory and pan-T-cell (CD3\u03b4<jats:sup>+<\/jats:sup>) and helper T-cell (CD45) responses on day 3 but later strongly exacerbated disease on day 10. Contrast analyses characterized severe<jats:italic>C. pneumoniae<\/jats:italic>disease as being a delayed-type hypersensitivity (DTH) response with increased lung macrophage and Th1 cell marker transcripts, increased Th1:Th2 ratios, and Th1 cytokine-driven inflammation. Results from functional analyses by DTH, enzyme-linked immunospot, and immunohistofluorescence assays were consistent with the results obtained by transcript analysis. Thus, chlamydial disease after secondary infection is a temporal dysregulation of the T-cell response characterized by a profoundly delayed T-helper cell response that results in a failure to eliminate the pathogen and provokes later pathological Th1 inflammation. This delayed T-cell response is under host genetic control and nutritional influence. The mechanism that temporally and quantitatively regulates the host T-cell population is the critical determinant in chlamydial pathogenesis.<\/jats:p>","DOI":"10.1128\/iai.00569-08","type":"journal-article","created":{"date-parts":[[2008,8,26]],"date-time":"2008-08-26T00:45:03Z","timestamp":1219711503000},"page":"4913-4923","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":3,"title":["Temporal Delay of Peak T-Cell Immunity Determines<i>Chlamydia pneumoniae<\/i>Pulmonary Disease in Mice"],"prefix":"10.1128","volume":"76","author":[{"given":"Chengming","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pathobiology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frederik W.","family":"van Ginkel","sequence":"additional","affiliation":[{"name":"Department of Pathobiology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teayoun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pathobiology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathobiology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yihang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathobiology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John C.","family":"Dennis","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Physiology, and Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, Alabama 36849-5519"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernhard","family":"Kaltenboeck","sequence":"additional","affiliation":[{"name":"Department of Pathobiology"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.2174\/1566524024605671"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0966-842X(94)90542-8"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)63775-5"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gene.6364285"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00691-06"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V87.5.2005.2005"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.13.7551"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1006\/mpat.1994.1023"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro796"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.25.14857"},{"key":"e_1_3_2_12_2","doi-asserted-by":"crossref","first-page":"3688","DOI":"10.4049\/jimmunol.138.11.3688","volume":"138","year":"1987","unstructured":"Cher, D. 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