{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T02:00:55Z","timestamp":1789437655531,"version":"build-2803163510"},"reference-count":59,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2004,10,1]],"date-time":"2004-10-01T00:00:00Z","timestamp":1096588800000},"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":[[2004,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Although both self- and pathogen-specific T cells can participate in tissue destruction, recent studies have proposed that after viral infection, bystander T cells of an irrelevant specificity can bypass peptide-MHC restriction and contribute to undesired immunopathological consequences. To evaluate the importance of this mechanism of immunopathogenesis, we determined the relative contributions of Ag-specific and bystander CD8+ T cells to the development of CNS disease. Using lymphocytic choriomeningitis virus (LCMV) as a stimulus for T cell recruitment into the CNS, we demonstrate that bystander CD8+ T cells with an activated surface phenotype can indeed be recruited into the CNS over a chronic time window. These cells become anatomically positioned in the CNS parenchyma, and a fraction aberrantly acquires the capacity to produce the effector cytokine, IFN-\u03b3. However, when directly compared with their virus-specific counterparts, the contribution of bystander T cells to CNS damage was insignificant in nature (even when specifically activated). Although bystander T cells alone failed to cause tissue injury, transferring as few as 1000 naive LCMV-specific CD8+ T cells into a restricted repertoire containing only bystander T cells was sufficient to induce immune-mediated pathology and reconstitute a fatal CNS disease. These studies underscore the importance of specific T cells in the development of immunopathology and subsequent disease. Because of highly restrictive constraints imposed by the host, it is more likely that specific, rather than nonspecific, bystander T cells are the active participants in T cell-mediated diseases that afflict humans.<\/jats:p>","DOI":"10.4049\/jimmunol.173.8.4779","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T22:29:16Z","timestamp":1398032956000},"page":"4779-4790","source":"Crossref","is-referenced-by-count":27,"title":["Rebuilding an Immune-Mediated Central Nervous System Disease: Weighing the Pathogenicity of Antigen-Specific versus Bystander T Cells"],"prefix":"10.1093","volume":"173","author":[{"given":"Dorian B","family":"McGavern","sequence":"first","affiliation":[{"name":"Department of Neuropharmacology, Division of Virology The Scripps Research Institute , La Jolla, CA 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phi","family":"Truong","sequence":"additional","affiliation":[{"name":"Department of Neuropharmacology, Division of Virology The Scripps Research Institute , La Jolla, CA 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2004,10,15]]},"reference":[{"key":"2026020214111409000_R1","first-page":"701","volume-title":"Nature","year":"1974"},{"key":"2026020214111409000_R2","first-page":"245","volume-title":"Structure","year":"1994"},{"key":"2026020214111409000_R3","first-page":"1947","volume-title":"Science","year":"1996"},{"key":"2026020214111409000_R4","first-page":"4289","volume-title":"J. 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