{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T21:47:59Z","timestamp":1792100879240,"version":"4.4.0"},"reference-count":78,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2019,3,1]],"date-time":"2019-03-01T00:00:00Z","timestamp":1551398400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Control of chronic CNS infection with the parasite Toxoplasma gondii requires ongoing T cell responses in the brain. Immunosuppressive cytokines are also important for preventing lethal immunopathology during chronic infection. To explore the loss of suppressive cytokines exclusively during the chronic phase of infection, we blocked IL-10R in chronically infected mice. Consistent with previous reports, IL-10R blockade led to severe, fatal tissue destruction associated with widespread changes in the inflammatory response, including increased APC activation, expansion of CD4+ T cells, and neutrophil recruitment to the brain. We then sought to identify regulatory mechanisms contributing to IL-10 production, focusing on ICOS, a molecule implicated in IL-10 production. Unexpectedly, ICOS ligand (ICOSL) blockade led to a local expansion of effector T cells in the brain without affecting IL-10 production or APC activation. Instead, we found that ICOSL blockade led to changes in T cells associated with their proliferation and survival. We observed increased expression of IL-2\u2013associated signaling molecules CD25, STAT5 phosphorylation, Ki67, and Bcl-2 in T cells in the brain, along with decreased apoptosis. Interestingly, increases in CD25 and Bcl-2 were not observed following IL-10R blockade. Also, unlike IL-10R blockade, ICOSL blockade led to an expansion of both CD8+ and CD4+ T cells in the brain, with no expansion of peripheral T cells or neutrophil recruitment to the brain and no severe tissue destruction. Overall, these results suggest that IL-10 and ICOS differentially regulate T cell responses in the brain during chronic T. gondii infection.<\/jats:p>","DOI":"10.4049\/jimmunol.1801229","type":"journal-article","created":{"date-parts":[[2019,2,4]],"date-time":"2019-02-04T15:25:17Z","timestamp":1549293917000},"page":"1755-1766","source":"Crossref","is-referenced-by-count":19,"title":["IL-10 and ICOS Differentially Regulate T Cell Responses in the Brain during Chronic\n                    <i>Toxoplasma gondii<\/i>\n                    Infection"],"prefix":"10.1093","volume":"202","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":"Samantha J","family":"Batista","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":"Katherine M","family":"Still","sequence":"additional","affiliation":[{"name":"Center for Brain Immunology and Glia, Department of Neuroscience, University of Virginia , Charlottesville, VA 22908"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1355-2109","authenticated-orcid":false,"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":[[2019,3,15]]},"reference":[{"key":"2025030417561155000_r1","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.it.2005.10.003","article-title":"Understanding the IL-23-IL-17 immune pathway","volume":"27","author":"McKenzie","year":"2006","journal-title":"Trends Immunol."},{"key":"2025030417561155000_r2","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1038\/nature06246","article-title":"Recognition of microorganisms and activation of the immune response","volume":"449","author":"Medzhitov","year":"2007","journal-title":"Nature"},{"key":"2025030417561155000_r3","doi-asserted-by":"crossref","first-page":"798","DOI":"10.4049\/jimmunol.157.2.798","article-title":"In the absence of endogenous IL-10, mice acutely infected with Toxoplasma gondii succumb to a lethal immune response dependent on CD4+ T cells and accompanied by overproduction of IL-12, IFN-gamma and TNF-alpha","volume":"157","author":"Gazzinelli","year":"1996","journal-title":"J. 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