{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T16:47:54Z","timestamp":1791478074896,"version":"4.3.4"},"reference-count":43,"publisher":"National Academy of Sciences","issue":"3","license":[{"start":{"date-parts":[[2024,1,8]],"date-time":"2024-01-08T00:00:00Z","timestamp":1704672000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2024,1,16]]},"abstract":"<jats:p>Epstein\u2013Barr virus (EBV) infection has long been associated with multiple sclerosis (MS), but the role of EBV in the pathogenesis of MS is not clear. Our hypothesis is that a major fraction of the expanded clones of T lymphocytes in the cerebrospinal fluid (CSF) are specific for autologous EBV-infected B cells. We obtained blood and CSF samples from eight relapsing-remitting patients in the process of diagnosis. We stimulated cells from the blood with autologous EBV-infected lymphoblastoid cell lines (LCL), EBV, varicella zoster virus, influenza, and candida and sorted the responding cells with flow cytometry after 6 d. We sequenced the RNA for T cell receptors (TCR) from CSF, unselected blood cells, and the antigen-specific cells. We used the TCR V\u03b2 CDR3 sequences from the antigen-specific cells to assign antigen specificity to the sequences from the CSF and blood. LCL-specific cells comprised 13.0 \u00b1 4.3% (mean \u00b1 SD) of the total reads present in CSF and 13.3 \u00b1 7.5% of the reads present in blood. The next most abundant antigen specificity was flu, which was 4.7 \u00b1 1.7% of the reads in the CSF and 9.3 \u00b1 6.6% in the blood. The prominence of LCL-specific reads was even more marked in the top 1% most abundant CSF clones with statistically significant 47% mean overlap with LCL. We conclude that LCL-specific sequences form a major portion of the TCR repertoire in both CSF and blood and that expanded clones specific for LCL are present in MS CSF. This has important implications for the pathogenesis of MS.<\/jats:p>","DOI":"10.1073\/pnas.2315857121","type":"journal-article","created":{"date-parts":[[2024,1,8]],"date-time":"2024-01-08T15:17:28Z","timestamp":1704727048000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":50,"title":["Expanded T lymphocytes in the cerebrospinal fluid of multiple sclerosis patients are specific for Epstein-Barr-virus-infected B cells"],"prefix":"10.1073","volume":"121","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4904-631X","authenticated-orcid":false,"given":"Assaf","family":"Gottlieb","sequence":"first","affiliation":[{"name":"Center for Precision Health, School of Biomedical Informatics, University of Texas Health Science Center at Houston, Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. Phuong T.","family":"Pham","sequence":"additional","affiliation":[{"name":"Division of Multiple Sclerosis and Neuroimmunology, Department of Neurology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerome G.","family":"Saltarrelli","sequence":"additional","affiliation":[{"name":"Department of Surgery, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6856-0811","authenticated-orcid":false,"given":"J. William","family":"Lindsey","sequence":"additional","affiliation":[{"name":"Division of Multiple Sclerosis and Neuroimmunology, Department of Neurology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2024,1,8]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1980.00500510052009"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1983.04050070036006"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1177\/1352458511408991"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000130496.51156.D7"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.937583"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0012496"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/ane.12417"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2004.048504"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181aa29fe"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abj8222"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04432-7"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.199"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.218"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2011.01.010"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI128475"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abb8786"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2008523117"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-14118-w"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btx286"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.11.7853"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.08.011"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2021.103282"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201444662"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1080\/13550280490261671"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0105434"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1177\/1352458515588581"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-017-1744-4"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21316"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clineuro.2013.12.020"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.03.047"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0192109"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000000466"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2023.578036"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awp200"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181d865a1"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.162.1.129"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1080\/13550280490499524"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1902623116"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-4141(199903)29:03<973::AID-IMMU973>3.0.CO;2-P"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.835763"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1002\/bimj.4710330314"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.2517-6161.1995.tb02031.x"},{"key":"e_1_3_4_43_2","doi-asserted-by":"crossref","unstructured":"A. Gottlieb J. W. Lindsey Expanded T lymphocytes in the cerebrospinal fluid of multiple sclerosis patients are specific for Epstein-Barr virus infected B cells. GEO. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE250037. 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