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In mice, infection with Toxoplasma gondii leads to a Th1-polarized parasite-specific effector T cell response in the brain. Similarly, Tregs in the CNS during T. gondii infection are Th1 polarized, as exemplified by their T-bet, CXCR3, and IFN-\u03b3 expression. Unlike effector CD4+ T cells, an MHC class II tetramer reagent specific for T. gondii did not recognize Tregs isolated from the CNS. Likewise, TCR sequencing revealed minimal overlap in TCR sequence between effector T cells and Tregs in the CNS. Whereas effector T cells are found in the brain parenchyma where parasites are present, Tregs were restricted to the meninges and perivascular spaces. The use of intravital imaging revealed that activated CD4+ T cells within the meninges were highly migratory, whereas Tregs moved more slowly and were found in close association with CD11c+ cells. To test whether the behavior of Tregs in the meninges is influenced by interactions with CD11c+ cells, mice were treated with anti\u2013LFA-1 Abs to reduce the number of CD11c+ cells in this space. The anti\u2013LFA-1 treatment led to fewer contacts between Tregs and the remaining CD11c+ cells and increased the speed of Treg migration. These data suggest that Tregs are anatomically restricted within the CNS, and their interaction with CD11c+ populations regulates their local behavior during T. gondii infection.<\/jats:p>","DOI":"10.4049\/jimmunol.1601581","type":"journal-article","created":{"date-parts":[[2017,4,8]],"date-time":"2017-04-08T00:30:29Z","timestamp":1491611429000},"page":"4054-4061","source":"Crossref","is-referenced-by-count":35,"title":["CD11c-Expressing Cells Affect Regulatory T Cell Behavior in the Meninges during Central Nervous System Infection"],"prefix":"10.1093","volume":"198","author":[{"given":"Carleigh A","family":"O\u2019Brien","sequence":"first","affiliation":[{"name":"Center for Brain Immunology and Glia, Department of Neuroscience, University of Virginia , Charlottesville, VA 22908"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Overall","sequence":"additional","affiliation":[{"name":"Center for Brain Immunology and Glia, Department of Neuroscience, University of Virginia , Charlottesville, VA 22908"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Konradt","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aisling C","family":"O\u2019Hara Hall","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1885-1850","authenticated-orcid":false,"given":"Nikolas W","family":"Hayes","sequence":"additional","affiliation":[{"name":"Center for Brain Immunology and Glia, Department of Neuroscience, University of Virginia , Charlottesville, VA 22908"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sagie","family":"Wagage","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beena","family":"John","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A","family":"Christian","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher A","family":"Hunter","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tajie H","family":"Harris","sequence":"additional","affiliation":[{"name":"Center for Brain Immunology and Glia, Department of Neuroscience, University of Virginia , Charlottesville, VA 22908"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,5,15]]},"reference":[{"key":"2025030615135031300_r1","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1016\/j.coi.2009.09.011","article-title":"Regulatory T cells and inhibitory cytokines in autoimmunity","volume":"21","author":"Bettini","year":"2009","journal-title":"Curr. 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