{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T09:56:56Z","timestamp":1789898216091,"version":"4.0.1"},"reference-count":0,"publisher":"Rockefeller University Press","issue":"5","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1995,11,1]]},"abstract":"<jats:p>Neurons have evolved strategies to evade immune surveillance that include an inability to synthesize the heavy chain of the class I major histocompatibility complex (MHC), proteins that are necessary for cytotoxic T lymphocyte (CTL) recognition of target cells. Multiple viruses have taken advantage of the lack of CTL-mediated recognition and killing of neurons by establishing persistent neuronal infections and thereby escaping attack by antiviral CTL. We have expressed a class I MHC molecule (Db) in neurons of transgenic mice using the neuron-specific enolase (NSE) promoter to determine the pathogenic consequences of CTL recognition of virally infected, MHC-expressing central nervous system (CNS) neurons. The NSE-Db transgene was expressed in H-2b founder mice, and transgene-derived messenger RNA was detected by reverse transcriptase-polymerase chain reaction in transgenic brains from several lines. Purified primary neurons from transgenic but not from nontransgenic mice adhered to coverslips coated with a conformation-dependent monoclonal antibody directed against the Dv molecule and presented viral peptide to CTL in an MHC-restricted manner, indicating that the Db molecule was expressed on transgenic neurons in a functional form. Transgenic mice infected with the neurotropic lymphocytic choriomeningitis virus (LCMV) and given anti-LCMV, MHC-restricted CTL displayed a high morbidity and mortality when compared with controls receiving MHC-mismatched CTL or expressing alternative transgenes. After CTL transfer, transgenic brains showed an increased number of CD8+ cells compared with nontransgenic controls as well as an increased rate of clearance of infectious virus from the CNS. Additionally, an increase in blood-brain barrier permeability was detected during viral clearance in NSE-Db transgenic mice and lasted several months after clearance of virus from neurons. In contrast, LCMV-infected, nontransgenic littermates and mice expressing other gene products from the NSE promoter showed no CNS disease, no increased intraparenchymal CTL, and no blood-brain barrier damage after the adoptive transfer of antiviral CTL. Our study indicates that viral infections and CTL-CNS interactions may induce blood-brain barrier disruptions and neurologic disease by a \"hit-and-run\" mechanism, triggering a cascade of pathogenic events that proceeds in the absence of continual viral stimulation.<\/jats:p>","DOI":"10.1084\/jem.182.5.1201","type":"journal-article","created":{"date-parts":[[2004,6,24]],"date-time":"2004-06-24T07:56:10Z","timestamp":1088063770000},"page":"1201-1212","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":102,"title":["Consequences of cytotoxic T lymphocyte interaction with major histocompatibility complex class I-expressing neurons in vivo."],"prefix":"10.1084","volume":"182","author":[{"given":"G F","family":"Rall","sequence":"first","affiliation":[{"name":"Scripps Research Institute, Department of Neuropharmacology, La Jolla, California 92037, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Mucke","sequence":"additional","affiliation":[{"name":"Scripps Research Institute, Department of Neuropharmacology, La Jolla, California 92037, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M B","family":"Oldstone","sequence":"additional","affiliation":[{"name":"Scripps Research Institute, Department of Neuropharmacology, La Jolla, California 92037, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[1995,11,1]]},"container-title":["The Journal of experimental medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/182\/5\/1201\/1677925\/1201.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/182\/5\/1201\/1677925\/1201.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T07:01:42Z","timestamp":1690268502000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jem\/article\/182\/5\/1201\/25758\/Consequences-of-cytotoxic-T-lymphocyte-interaction"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1995,11,1]]},"references-count":0,"journal-issue":{"issue":"5","published-print":{"date-parts":[[1995,11,1]]}},"URL":"https:\/\/doi.org\/10.1084\/jem.182.5.1201","relation":{},"ISSN":["0022-1007","1540-9538"],"issn-type":[{"value":"0022-1007","type":"print"},{"value":"1540-9538","type":"electronic"}],"subject":[],"published":{"date-parts":[[1995,11,1]]}}}