{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:32:32Z","timestamp":1791297152824,"version":"4.1.0"},"reference-count":62,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2015,11,1]],"date-time":"2015-11-01T00:00:00Z","timestamp":1446336000000},"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":[[2015,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Much of our understanding of CNS immunity has been gained from models involving pathological inflammation. Attenuated rabies viruses (RABV) are unique tools to study CNS immunity in the absence of conventional inflammatory mechanisms, as they spread from the site of inoculation to the CNS transaxonally, thereby bypassing the blood\u2013brain barrier (BBB), and are cleared without neutrophil or monocyte infiltration. To better understand the role of CD4 T cell subsets in the clearance of the virus from CNS tissues, we examined the development of antiviral immunity in wild-type (WT) and T-bet knockout mice (T-bet\u2212\/\u2212), which lack Th1 cells. Early control of RABV replication in the CNS tissues of WT mice is associated with the production of IFN-\u03b3, with antiviral effects likely mediated through the enhanced expression of type I IFNs. Of interest, IFN-\u03b1 and -\u03b3 are overexpressed in the infected T-bet\u2212\/\u2212 by comparison with WT CNS tissues, and the initial control of RABV infection is similar. Ultimately, attenuated RABV are cleared from the CNS tissues of WT mice by Ab locally produced by the activities of infiltrating T and B cells. Although T and B cell infiltration into the CNS of infected T-bet\u2212\/\u2212 mice is comparable, their activities are not, the consequence being delayed, low-level Ab production and prolonged RABV replication. More importantly, neither T-bet\u2212\/\u2212 mice immunized with an attenuated virus, nor WT mice with Th2 RABV-specific immunity induced by immunization with inactivated virus, are protected in the long term against challenge with a pathogenic RABV.<\/jats:p>","DOI":"10.4049\/jimmunol.1501274","type":"journal-article","created":{"date-parts":[[2015,9,26]],"date-time":"2015-09-26T00:28:35Z","timestamp":1443227315000},"page":"4358-4368","source":"Crossref","is-referenced-by-count":33,"title":["T-bet Is Required for the Rapid Clearance of Attenuated Rabies Virus from Central Nervous System Tissue"],"prefix":"10.1093","volume":"195","author":[{"given":"Aurore","family":"Lebrun","sequence":"first","affiliation":[{"name":"Department of Cancer Biology, Thomas Jefferson University , Philadelphia, PA 19107"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Portocarrero","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, Thomas Jefferson University , Philadelphia, PA 19107"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhonda B","family":"Kean","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, Thomas Jefferson University , Philadelphia, PA 19107"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darryll A","family":"Barkhouse","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, Thomas Jefferson University , Philadelphia, PA 19107"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milosz","family":"Faber","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Thomas Jefferson University , Philadelphia, PA 19107"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D Craig","family":"Hooper","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, Thomas Jefferson University , Philadelphia, PA 19107"},{"name":"Department of Neurological Surgery, Thomas Jefferson University , Philadelphia, PA 19107"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,11,1]]},"reference":[{"key":"2025030704211827100_r1","first-page":"H1197","article-title":"Albumin outflow into deep cervical lymph from different regions of rabbit brain","volume":"261","author":"Yamada","year":"1991","journal-title":"Am. 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