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Recombination activating gene 1<jats:sup>\u2212\/\u2212<\/jats:sup> mice failed to block the mutant <jats:italic>Chlamydia<\/jats:italic> spreading, while mice deficient in toll\u2010like receptors, myeloid differentiation primary response 88 or stimulator of interferon genes still blocked the spreading, suggesting that the intestinal barrier function is dependent on lymphocytes that express antigen receptors. Mice deficient in CD4, but not CD8 nor \u03bc chain failed to prevent the chlamydial spreading, indicating a protective role of CD4<jats:sup>+<\/jats:sup> cells in the intestinal barrier. Consistently, adoptive transfer of CD4<jats:sup>+<\/jats:sup> T cells reconstituted the intestinal barrier in CD4<jats:sup>\u2010\/\u2010<\/jats:sup> mice. More importantly, CD4<jats:sup>+<\/jats:sup> but not CD8<jats:sup>+<\/jats:sup> T cells nor B cells restored the intestinal barrier function in recombination activating gene 1<jats:sup>\u2212\/\u2212<\/jats:sup> mice. Thus, CD4<jats:sup>+<\/jats:sup> T cells are necessary and sufficient for maintaining the intestinal barrier function, indicating that the spread of an intracellular bacterium from the small intestine to the large intestine is regulated by an immunological barrier. This study has also laid a foundation for further illuminating the mechanisms by which a CD4<jats:sup>+<\/jats:sup> T cell\u2010dependent intestinal barrier regulates bacterial spreading in the gut.<\/jats:p>","DOI":"10.1111\/imcb.12446","type":"journal-article","created":{"date-parts":[[2021,2,10]],"date-time":"2021-02-10T10:02:29Z","timestamp":1612951349000},"page":"611-621","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Regulation of <i>Chlamydia<\/i> spreading from the small intestine to the large intestine via an immunological barrier"],"prefix":"10.1111","volume":"99","author":[{"given":"Conghui","family":"He","sequence":"first","affiliation":[{"name":"Department of Microbiology, Immunology and Molecular Genetics University of Texas Health Science Center at San Antonio San Antonio TX USA"},{"name":"Department of Immunology Medical College of Hebei North University Zhangjiakou Hebei China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Molecular Genetics University of Texas Health Science Center at San Antonio San Antonio TX USA"},{"name":"Department of Immunology, Xiangya School of Medicine Central South University Changsha City Hunan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhi","family":"Huo","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Molecular Genetics University of Texas Health Science Center at San Antonio San Antonio TX USA"},{"name":"Department of Immunology, Xiangya School of Medicine Central South University Changsha City Hunan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Immunology, Xiangya School of Medicine Central South University Changsha City Hunan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tianjun","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Immunology Medical College of Hebei North University Zhangjiakou Hebei China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao\u2010Dong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Molecular Genetics University of Texas Health Science Center at San Antonio San Antonio TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guangming","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Molecular Genetics University of Texas Health Science Center at San Antonio San Antonio TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,3,3]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0b013e3182519326"},{"key":"e_1_2_7_3_1","unstructured":"Centers for Disease Control and Prevention C.Sexually Transmitted Disease Surveillance 2016. 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