{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T07:38:23Z","timestamp":1792222703944,"version":"4.4.0"},"reference-count":62,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2009,5,1]],"date-time":"2009-05-01T00:00:00Z","timestamp":1241136000000},"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":[[2009,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The neurotropic coronavirus JHM strain of mouse hepatitis virus persists in oligodendroglia despite the presence of virus-specific CD8 T cells. Expression of programmed death 1 (PD-1) and B7-H1 were studied during acute and persistent infection to examine whether this negative regulatory mechanism contributes to CNS viral persistence. The majority of CNS-infiltrating CD8 T cells expressed PD-1, with the highest levels on virus-specific CD8 T cells. Moreover, despite control of infectious virus, CD8 T cells within the CNS of persistently infected mice maintained high PD-1 expression. Analysis of virus-susceptible target cells in vivo revealed that B7-H1 expression was regulated in a cell type-dependent manner. Oligodendroglia and microglia up-regulated B7-H1 following infection; however, although B7-H1 expression on oligodendroglia was prominent and sustained, it was significantly reduced and transient on microglia. Infection of mice deficient in the IFN-\u03b3 or IFN-\u03b1\/\u03b2 receptor demonstrated that B7-H1 expression on oligodendroglia is predominantly regulated by IFN-\u03b3. Ab blockade of B7-H1 on oligodendroglia in vitro enhanced IFN-\u03b3 secretion by virus-specific CD8 T cells. More efficient virus control within the CNS of B7-H1-deficient mice confirmed inhibition of CD8 T cell function in vivo. Nevertheless, the absence of B7-H1 significantly increased morbidity without altering demyelination. These data are the first to demonstrate glia cell type-dependent B7-H1 regulation in vivo, resulting in adverse effects on antiviral CD8 T cell function. However, the beneficial role of PD-1:B7-H1 interactions in limiting morbidity highlights the need to evaluate tissue-specific intervention strategies.<\/jats:p>","DOI":"10.4049\/jimmunol.0803557","type":"journal-article","created":{"date-parts":[[2009,4,21]],"date-time":"2009-04-21T01:07:38Z","timestamp":1240276058000},"page":"5430-5438","source":"Crossref","is-referenced-by-count":77,"title":["Target-Dependent B7-H1 Regulation Contributes to Clearance of Central Nervous Sysyem Infection and Dampens Morbidity"],"prefix":"10.1093","volume":"182","author":[{"given":"Timothy W","family":"Phares","sequence":"first","affiliation":[{"name":"Department of Neurosciences, Lerner Research Institute, The Cleveland Clinic , Cleveland, OH 44195"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandran","family":"Ramakrishna","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Lerner Research Institute, The Cleveland Clinic , Cleveland, OH 44195"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel I","family":"Parra","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Lerner Research Institute, The Cleveland Clinic , Cleveland, OH 44195"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Epstein","sequence":"additional","affiliation":[{"name":"Department of Pathology, Keck School of Medicine, University of Southern California , Los Angeles, CA 90033"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lieping","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Oncology, Johns Hopkins University School of Medicine , Baltimore, MD 21231"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roscoe","family":"Atkinson","sequence":"additional","affiliation":[{"name":"Department of Pathology, Keck School of Medicine, University of Southern California , Los Angeles, CA 90033"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen A","family":"Stohlman","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Lerner Research Institute, The Cleveland Clinic , Cleveland, OH 44195"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelia C","family":"Bergmann","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Lerner Research Institute, The Cleveland Clinic , Cleveland, OH 44195"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,5,1]]},"reference":[{"key":"2026012807021794500_R1","first-page":"258","article-title":"Molecular and cellular permeability control at the blood-brain barrier.","volume-title":"Brain Res. 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