{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T23:55:23Z","timestamp":1793663723782,"version":"4.5.1"},"reference-count":73,"publisher":"Springer Science and Business Media LLC","issue":"7916","license":[{"start":{"date-parts":[[2022,6,22]],"date-time":"2022-06-22T00:00:00Z","timestamp":1655856000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2022,6,22]],"date-time":"2022-06-22T00:00:00Z","timestamp":1655856000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nature"],"published-print":{"date-parts":[[2022,6,30]]},"DOI":"10.1038\/s41586-022-04844-5","type":"journal-article","created":{"date-parts":[[2022,6,22]],"date-time":"2022-06-22T12:37:07Z","timestamp":1655901427000},"page":"945-952","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":91,"title":["Clonally expanded CD8 T cells characterize amyotrophic lateral sclerosis-4"],"prefix":"10.1038","volume":"606","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4173-4521","authenticated-orcid":false,"given":"Laura","family":"Campisi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5659-1140","authenticated-orcid":false,"given":"Shahab","family":"Chizari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2234-2602","authenticated-orcid":false,"given":"Jessica S. Y.","family":"Ho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasia","family":"Gromova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1927-264X","authenticated-orcid":false,"given":"Frederick J.","family":"Arnold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorena","family":"Mosca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueyan","family":"Mei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yesai","family":"Fstkchyan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denis","family":"Torre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cindy","family":"Beharry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Garcia-Forn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Jim\u00e9nez-Alc\u00e1zar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9127-292X","authenticated-orcid":false,"given":"Vlad A.","family":"Korben","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack","family":"Prazich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3439-7347","authenticated-orcid":false,"given":"Zahi A.","family":"Fayad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus M.","family":"Seldin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9383-6883","authenticated-orcid":false,"given":"Silvia","family":"De Rubeis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig L.","family":"Bennett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7158-5243","authenticated-orcid":false,"given":"Lyle W.","family":"Ostrow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Lunetta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Squatrito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minji","family":"Byun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil A.","family":"Shneider","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1103-5922","authenticated-orcid":false,"given":"Ning","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert R.","family":"La Spada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3376-0922","authenticated-orcid":false,"given":"Ivan","family":"Marazzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,6,22]]},"reference":[{"key":"4844_CR1","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1056\/NEJMra1603471","volume":"377","author":"RH Brown","year":"2017","unstructured":"Brown, R. H. & Al-Chalabi, A. Amyotrophic lateral sclerosis. N. Engl. J. Med. 377, 162\u2013172 (2017).","journal-title":"N. Engl. J. Med."},{"key":"4844_CR2","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1007\/s00401-018-1933-9","volume":"137","author":"ME McCauley","year":"2019","unstructured":"McCauley, M. E. & Baloh, R. H. Inflammation in ALS\/FTD pathogenesis. Acta Neuropathol. 137, 715\u2013730 (2019).","journal-title":"Acta Neuropathol"},{"key":"4844_CR3","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1002\/ana.25681","volume":"87","author":"C Grunseich","year":"2020","unstructured":"Grunseich, C. et al. Clinical and molecular aspects of senataxin mutations in amyotrophic lateral sclerosis 4. Ann. Neurol. 87, 547\u2013555 (2020).","journal-title":"Ann. Neurol."},{"key":"4844_CR4","doi-asserted-by":"publisher","first-page":"1389","DOI":"10.1126\/science.1123511","volume":"312","author":"S Boillee","year":"2006","unstructured":"Boillee, S. et al. Onset and progression in inherited ALS determined by motor neurons and microglia. Science 312, 1389\u20131392 (2006).","journal-title":"Science"},{"key":"4844_CR5","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1038\/nn2047","volume":"11","author":"K Yamanaka","year":"2008","unstructured":"Yamanaka, K. et al. Astrocytes as determinants of disease progression in inherited amyotrophic lateral sclerosis. Nat. Neurosci. 11, 251\u2013253 (2008).","journal-title":"Nat. Neurosci."},{"key":"4844_CR6","doi-asserted-by":"publisher","first-page":"3063","DOI":"10.1172\/JCI62636","volume":"122","author":"O Butovsky","year":"2012","unstructured":"Butovsky, O. et al. Modulating inflammatory monocytes with a unique microRNA gene signature ameliorates murine ALS. J. Clin. Invest. 122, 3063\u20133087 (2012).","journal-title":"J. Clin. Invest."},{"key":"4844_CR7","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1038\/s41586-020-2625-x","volume":"585","author":"ME McCauley","year":"2020","unstructured":"McCauley, M. E. et al. C9orf72 in myeloid cells suppresses STING-induced inflammation. Nature 585, 96\u2013101 (2020).","journal-title":"Nature"},{"key":"4844_CR8","doi-asserted-by":"publisher","first-page":"1324","DOI":"10.1126\/science.aaf1064","volume":"351","author":"JG O'Rourke","year":"2016","unstructured":"O\u2019Rourke, J. G. et al. C9orf72 is required for proper macrophage and microglial function in mice. Science 351, 1324\u20131329 (2016).","journal-title":"Science"},{"key":"4844_CR9","doi-asserted-by":"publisher","DOI":"10.1038\/srep23204","volume":"6","author":"A Atanasio","year":"2016","unstructured":"Atanasio, A. et al. C9orf72 ablation causes immune dysregulation characterized by leukocyte expansion, autoantibody production, and glomerulonephropathy in mice. Sci. Rep. 6, 23204 (2016).","journal-title":"Sci. Rep."},{"key":"4844_CR10","doi-asserted-by":"publisher","first-page":"347ra393","DOI":"10.1126\/scitranslmed.aaf6038","volume":"8","author":"A Burberry","year":"2016","unstructured":"Burberry, A. et al. Loss-of-function mutations in the C9ORF72 mouse ortholog cause fatal autoimmune disease. Sci. Transl. Med. 8, 347ra393 (2016).","journal-title":"Sci. Transl. Med."},{"key":"4844_CR11","doi-asserted-by":"publisher","DOI":"10.1186\/s13041-017-0287-x","volume":"10","author":"JA Oakes","year":"2017","unstructured":"Oakes, J. A., Davies, M. C. & Collins, M. O. TBK1: a new player in ALS linking autophagy and neuroinflammation. Mol. Brain 10, 5 (2017).","journal-title":"Mol. Brain"},{"key":"4844_CR12","doi-asserted-by":"publisher","first-page":"1493","DOI":"10.1084\/jem.20161524","volume":"214","author":"Y Xiao","year":"2017","unstructured":"Xiao, Y. et al. The kinase TBK1 functions in dendritic cells to regulate T cell homeostasis, autoimmunity, and antitumor immunity. J. Exp. Med. 214, 1493\u20131507 (2017).","journal-title":"J. Exp. Med."},{"key":"4844_CR13","doi-asserted-by":"publisher","first-page":"e1003435","DOI":"10.1371\/journal.pgen.1003435","volume":"9","author":"OJ Becherel","year":"2013","unstructured":"Becherel, O. J. et al. Senataxin plays an essential role with DNA damage response proteins in meiotic recombination and gene silencing. PLoS Genet. 9, e1003435 (2013).","journal-title":"PLoS Genet."},{"key":"4844_CR14","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1038\/ni.3132","volume":"16","author":"MS Miller","year":"2015","unstructured":"Miller, M. S. et al. Senataxin suppresses the antiviral transcriptional response and controls viral biogenesis. Nat. Immunol. 16, 485\u2013494 (2015).","journal-title":"Nat. Immunol."},{"key":"4844_CR15","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1007\/s00401-018-1852-9","volume":"136","author":"CL Bennett","year":"2018","unstructured":"Bennett, C. L. et al. Senataxin mutations elicit motor neuron degeneration phenotypes and yield TDP-43 mislocalization in ALS4 mice and human patients. Acta Neuropathol. 136, 425\u2013443 (2018).","journal-title":"Acta Neuropathol."},{"key":"4844_CR16","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1016\/j.cell.2012.07.007","volume":"150","author":"VA Rathinam","year":"2012","unstructured":"Rathinam, V. A. et al. TRIF licenses caspase-11-dependent NLRP3 inflammasome activation by Gram-negative bacteria. Cell 150, 606\u2013619 (2012).","journal-title":"Cell"},{"key":"4844_CR17","doi-asserted-by":"publisher","first-page":"636","DOI":"10.1016\/j.cell.2020.09.020","volume":"183","author":"CH Yu","year":"2020","unstructured":"Yu, C. H. et al. TDP-43 triggers mitochondrial DNA release via mPTP to activate cGAS\/STING in ALS. Cell 183, 636\u2013649 (2020).","journal-title":"Cell"},{"key":"4844_CR18","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1038\/s41586-019-1895-7","volume":"577","author":"D Gate","year":"2020","unstructured":"Gate, D. et al. Clonally expanded CD8 T cells patrol the cerebrospinal fluid in Alzheimer\u2019s disease. Nature 577, 399\u2013404 (2020).","journal-title":"Nature"},{"key":"4844_CR19","doi-asserted-by":"publisher","first-page":"868","DOI":"10.1126\/science.abf7266","volume":"374","author":"D Gate","year":"2021","unstructured":"Gate, D. et al. CD4+ T cells contribute to neurodegeneration in Lewy body dementia. Science 374, 868\u2013874 (2021).","journal-title":"Science"},{"key":"4844_CR20","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-15626-w","volume":"11","author":"CS Lindestam Arlehamn","year":"2020","unstructured":"Lindestam Arlehamn, C. S. et al. \u03b1-Synuclein-specific T cell reactivity is associated with preclinical and early Parkinson's disease. Nat. Commun. 11, 1875 (2020).","journal-title":"Nat. Commun."},{"key":"4844_CR21","doi-asserted-by":"publisher","first-page":"656","DOI":"10.1038\/nature22815","volume":"546","author":"D Sulzer","year":"2017","unstructured":"Sulzer, D. et al. T cells from patients with Parkinson\u2019s disease recognize \u03b1-synuclein peptides. Nature 546, 656\u2013661 (2017).","journal-title":"Nature"},{"key":"4844_CR22","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1146\/annurev-med-012017-043208","volume":"69","author":"M Hashimoto","year":"2018","unstructured":"Hashimoto, M. et al. CD8 T cell exhaustion in chronic infection and cancer: opportunities for interventions. Annu. Rev. Med. 69, 301\u2013318 (2018).","journal-title":"Annu. Rev. Med."},{"key":"4844_CR23","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1038\/nm.4022","volume":"22","author":"K Baruch","year":"2016","unstructured":"Baruch, K. et al. PD-1 immune checkpoint blockade reduces pathology and improves memory in mouse models of Alzheimer\u2019s disease. Nat. Med. 22, 135\u2013137 (2016).","journal-title":"Nat. Med."},{"key":"4844_CR24","doi-asserted-by":"publisher","first-page":"2961","DOI":"10.4049\/jimmunol.1400003","volume":"192","author":"JM Schenkel","year":"2014","unstructured":"Schenkel, J. M., Fraser, K. A. & Masopust, D. Cutting edge: resident memory CD8 T cells occupy frontline niches in secondary lymphoid organs. J. Immunol. 192, 2961\u20132964 (2014).","journal-title":"J. Immunol."},{"key":"4844_CR25","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1084\/jem.177.1.57","volume":"177","author":"JL Baron","year":"1993","unstructured":"Baron, J. L., Madri, J. A., Ruddle, N. H., Hashim, G. & Janeway, C. A. Jr Surface expression of alpha 4 integrin by CD4 T cells is required for their entry into brain parenchyma. J. Exp. Med. 177, 57\u201368 (1993).","journal-title":"J. Exp. Med."},{"key":"4844_CR26","doi-asserted-by":"publisher","first-page":"1192","DOI":"10.4049\/jimmunol.1100695","volume":"187","author":"KG Young","year":"2011","unstructured":"Young, K. G., Maclean, S., Dudani, R., Krishnan, L. & Sad, S. CD8+ T cells primed in the periphery provide time-bound immune-surveillance to the central nervous system. J. Immunol. 187, 1192\u20131200 (2011).","journal-title":"J. Immunol."},{"key":"4844_CR27","doi-asserted-by":"publisher","first-page":"1084","DOI":"10.1038\/ni.3512","volume":"17","author":"L Campisi","year":"2016","unstructured":"Campisi, L. et al. Apoptosis in response to microbial infection induces autoreactive TH17 cells. Nat. Immunol. 17, 1084\u20131092 (2016).","journal-title":"Nat. Immunol."},{"key":"4844_CR28","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1146\/annurev.immunol.24.021605.090727","volume":"24","author":"A Ma","year":"2006","unstructured":"Ma, A., Koka, R. & Burkett, P. Diverse functions of IL-2, IL-15, and IL-7 in lymphoid homeostasis. Annu. Rev. Immunol. 24, 657\u2013679 (2006).","journal-title":"Annu. Rev. Immunol."},{"key":"4844_CR29","doi-asserted-by":"publisher","first-page":"eaba7918","DOI":"10.1126\/sciimmunol.aba7918","volume":"5","author":"T Sekine","year":"2020","unstructured":"Sekine, T. et al. TOX is expressed by exhausted and polyfunctional human effector memory CD8+ T cells. Sci. Immunol. 5, eaba7918 (2020).","journal-title":"Sci. Immunol."},{"key":"4844_CR30","doi-asserted-by":"publisher","first-page":"1185","DOI":"10.1172\/JCI200112516","volume":"108","author":"S Markovic-Plese","year":"2001","unstructured":"Markovic-Plese, S., Cortese, I., Wandinger, K. P., McFarland, H. F. & Martin, R. CD4+CD28\u2212 costimulation-independent T cells in multiple sclerosis. J. Clin. Invest. 108, 1185\u20131194 (2001).","journal-title":"J. Clin. Invest."},{"key":"4844_CR31","doi-asserted-by":"publisher","first-page":"2027","DOI":"10.1172\/JCI118638","volume":"97","author":"D Schmidt","year":"1996","unstructured":"Schmidt, D., Goronzy, J. J. & Weyand, C. M. CD4+ CD7- CD28- T cells are expanded in rheumatoid arthritis and are characterized by autoreactivity. J. Clin. Invest. 97, 2027\u20132037 (1996).","journal-title":"J. Clin. Invest."},{"key":"4844_CR32","doi-asserted-by":"crossref","unstructured":"Gearty, S. V. et al. An autoimmune stem-like CD8 T cell population drives type 1 diabetes. Nature 602, 156\u2013161 (2022).","DOI":"10.1038\/s41586-021-04248-x"},{"key":"4844_CR33","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21109-3","volume":"12","author":"N Page","year":"2021","unstructured":"Page, N. et al. Persistence of self-reactive CD8+ T cells in the CNS requires TOX-dependent chromatin remodeling. Nat. Commun. 12, 1009 (2021).","journal-title":"Nat. Commun."},{"key":"4844_CR34","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1038\/s41586-019-1362-5","volume":"571","author":"BW Dulken","year":"2019","unstructured":"Dulken, B. W. et al. Single-cell analysis reveals T cell infiltration in old neurogenic niches. Nature 571, 205\u2013210 (2019).","journal-title":"Nature"},{"key":"4844_CR35","doi-asserted-by":"publisher","first-page":"1067","DOI":"10.1084\/jem.20091419","volume":"207","author":"NC Derecki","year":"2010","unstructured":"Derecki, N. C. et al. Regulation of learning and memory by meningeal immunity: a key role for IL-4. J. Exp. Med. 207, 1067\u20131080 (2010).","journal-title":"J. Exp. Med."},{"key":"4844_CR36","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1038\/nrn.2017.39","volume":"18","author":"AJ Filiano","year":"2017","unstructured":"Filiano, A. J., Gadani, S. P. & Kipnis, J. How and why do T cells and their derived cytokines affect the injured and healthy brain? Nat. Rev. Neurosci. 18, 375\u2013384 (2017).","journal-title":"Nat. Rev. Neurosci."},{"key":"4844_CR37","doi-asserted-by":"publisher","first-page":"766","DOI":"10.1126\/science.aag2638","volume":"353","author":"J Kipnis","year":"2016","unstructured":"Kipnis, J. Multifaceted interactions between adaptive immunity and the central nervous system. Science 353, 766\u2013771 (2016).","journal-title":"Science"},{"key":"4844_CR38","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1016\/j.copbio.2020.07.010","volume":"65","author":"J Chiffelle","year":"2020","unstructured":"Chiffelle, J. et al. T-cell repertoire analysis and metrics of diversity and clonality. Curr. Opin. Biotechnol. 65, 284\u2013295 (2020).","journal-title":"Curr. Opin. Biotechnol."},{"key":"4844_CR39","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-03731-w","volume":"9","author":"B Oldrini","year":"2018","unstructured":"Oldrini, B. et al. Somatic genome editing with the RCAS-TVA-CRISPR-Cas9 system for precision tumor modeling. Nat. Commun. 9, 1466 (2018).","journal-title":"Nat. Commun."},{"key":"4844_CR40","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1016\/j.ccell.2018.07.001","volume":"34","author":"A Kahles","year":"2018","unstructured":"Kahles, A. et al. Comprehensive analysis of alternative splicing across tumors from 8,705 patients. Cancer Cell 34, 211\u2013224 (2018).","journal-title":"Cancer Cell"},{"key":"4844_CR41","doi-asserted-by":"publisher","first-page":"713540","DOI":"10.3389\/fimmu.2021.713540","volume":"12","author":"P Ren","year":"2021","unstructured":"Ren, P. et al. Alternative splicing: a new cause and potential therapeutic target in autoimmune disease. Front. Immunol. 12, 713540 (2021).","journal-title":"Front. Immunol."},{"key":"4844_CR42","doi-asserted-by":"publisher","first-page":"5414","DOI":"10.4049\/jimmunol.170.11.5414","volume":"170","author":"Z Kurepa","year":"2003","unstructured":"Kurepa, Z., Su, J. & Forman, J. Memory phenotype of CD8+ T cells in MHC class Ia-deficient mice. J. Immunol. 170, 5414\u20135420 (2003).","journal-title":"J. Immunol."},{"key":"4844_CR43","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1038\/s41591-021-01615-z","volume":"28","author":"VA Korben","year":"2022","unstructured":"Korben, V. A., Lyashchenko, A. K., Blanco-Redondo, B., Jafar-Nejad, P. & Shneider, N. A. Antisense oligonucleotide silencing of FUS expression as a therapeutic approach in amyotrophic lateral sclerosis. Nat. Med. 28, 104\u2013116 (2022).","journal-title":"Nat. Med."},{"key":"4844_CR44","doi-asserted-by":"publisher","first-page":"1772","DOI":"10.1126\/science.8209258","volume":"264","author":"ME Gurney","year":"1994","unstructured":"Gurney, M. E. et al. Motor neuron degeneration in mice that express a human Cu,Zn superoxide dismutase mutation. Science 264, 1772\u20131775 (1994).","journal-title":"Science"},{"key":"4844_CR45","doi-asserted-by":"publisher","first-page":"3155","DOI":"10.1073\/pnas.93.7.3155","volume":"93","author":"PH Tu","year":"1996","unstructured":"Tu, P. H. et al. Transgenic mice carrying a human mutant superoxide dismutase transgene develop neuronal cytoskeletal pathology resembling human amyotrophic lateral sclerosis lesions. Proc. Natl Acad. Sci. USA 93, 3155\u20133160 (1996).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"4844_CR46","doi-asserted-by":"publisher","first-page":"708","DOI":"10.1038\/44385","volume":"401","author":"F Sallusto","year":"1999","unstructured":"Sallusto, F., Lenig, D., Forster, R., Lipp, M. & Lanzavecchia, A. Two subsets of memory T lymphocytes with distinct homing potentials and effector functions. Nature 401, 708\u2013712 (1999).","journal-title":"Nature"},{"key":"4844_CR47","doi-asserted-by":"publisher","first-page":"eaan8664","DOI":"10.1126\/sciimmunol.aan8664","volume":"3","author":"VS Patil","year":"2018","unstructured":"Patil, V. S. et al. Precursors of human CD4+ cytotoxic T lymphocytes identified by single-cell transcriptome analysis. Sci. Immunol. 3, eaan8664 (2018).","journal-title":"Sci. Immunol."},{"key":"4844_CR48","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1038\/ng.3822","volume":"49","author":"RO Emerson","year":"2017","unstructured":"Emerson, R. O. et al. Immunosequencing identifies signatures of cytomegalovirus exposure history and HLA-mediated effects on the T cell repertoire. Nat. Genet. 49, 659\u2013665 (2017).","journal-title":"Nat. Genet."},{"key":"4844_CR49","doi-asserted-by":"publisher","first-page":"2924","DOI":"10.1093\/bioinformatics\/btx286","volume":"33","author":"N Tickotsky","year":"2017","unstructured":"Tickotsky, N., Sagiv, T., Prilusky, J., Shifrut, E. & Friedman, N. McPAS-TCR: a manually curated catalogue of pathology-associated T cell receptor sequences. Bioinformatics 33, 2924\u20132929 (2017).","journal-title":"Bioinformatics"},{"key":"4844_CR50","doi-asserted-by":"publisher","first-page":"2099","DOI":"10.1128\/JVI.73.3.2099-2108.1999","volume":"73","author":"MP Weekes","year":"1999","unstructured":"Weekes, M. P., Wills, M. R., Mynard, K., Carmichael, A. J. & Sissons, J. G. The memory cytotoxic T-lymphocyte (CTL) response to human cytomegalovirus infection contains individual peptide-specific CTL clones that have undergone extensive expansion in vivo. J. Virol. 73, 2099\u20132108 (1999).","journal-title":"J. Virol."},{"key":"4844_CR51","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1038\/s41586-018-0540-1","volume":"562","author":"D Latorre","year":"2018","unstructured":"Latorre, D. et al. T cells in patients with narcolepsy target self-antigens of hypocretin neurons. Nature 562, 63\u201368 (2018).","journal-title":"Nature"},{"key":"4844_CR52","doi-asserted-by":"publisher","first-page":"1488","DOI":"10.1111\/ajt.12736","volume":"14","author":"L Campisi","year":"2014","unstructured":"Campisi, L., Cummings, R. J. & Blander, J. M. Death-defining immune responses after apoptosis. Am. J. Transplant. 14, 1488\u20131498 (2014).","journal-title":"Am. J. Transplant."},{"key":"4844_CR53","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1038\/s41590-020-00816-x","volume":"22","author":"CM Weyand","year":"2021","unstructured":"Weyand, C. M. & Goronzy, J. J. The immunology of rheumatoid arthritis. Nat. Immunol. 22, 10\u201318 (2021).","journal-title":"Nat. Immunol."},{"key":"4844_CR54","doi-asserted-by":"publisher","first-page":"303","DOI":"10.3389\/fimmu.2019.00303","volume":"10","author":"F Garretti","year":"2019","unstructured":"Garretti, F., Agalliu, D., Lindestam Arlehamn, C. S., Sette, A. & Sulzer, D. Autoimmunity in Parkinson\u2019s disease: the role of \u03b1-synuclein-specific T cells. Front. Immunol. 10, 303 (2019).","journal-title":"Front. Immunol."},{"key":"4844_CR55","doi-asserted-by":"publisher","first-page":"1539","DOI":"10.1093\/brain\/122.8.1539","volume":"122","author":"BA Rabin","year":"1999","unstructured":"Rabin, B. A. et al. Autosomal dominant juvenile amyotrophic lateral sclerosis. Brain 122, 1539\u20131550 (1999).","journal-title":"Brain"},{"key":"4844_CR56","doi-asserted-by":"publisher","first-page":"1507","DOI":"10.1038\/nprot.2006.268","volume":"1","author":"L Lamoreaux","year":"2006","unstructured":"Lamoreaux, L., Roederer, M. & Koup, R. Intracellular cytokine optimization and standard operating procedure. Nat. Protoc. 1, 1507\u20131516 (2006).","journal-title":"Nat. Protoc."},{"key":"4844_CR57","doi-asserted-by":"publisher","first-page":"e2307","DOI":"10.21769\/BioProtoc.2307","volume":"7","author":"L Campisi","year":"2017","unstructured":"Campisi, L. In vitro antigen-presentation assay for self- and microbial-derived antigens. Bio. Protoc. 7, e2307 (2017).","journal-title":"Bio. Protoc."},{"key":"4844_CR58","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1038\/nprot.2017.155","volume":"13","author":"B Korin","year":"2018","unstructured":"Korin, B., Dubovik, T. & Rolls, A. Mass cytometry analysis of immune cells in the brain. Nat. Protoc. 13, 377\u2013391 (2018).","journal-title":"Nat. Protoc."},{"key":"4844_CR59","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1007\/978-1-4939-9167-9_8","volume":"1960","author":"YS Tan","year":"2019","unstructured":"Tan, Y. S. & Lei, Y. L. Isolation of tumor-infiltrating lymphocytes by ficoll-paque density gradient centrifugation. Methods Mol. Biol. 1960, 93\u201399 (2019).","journal-title":"Methods Mol. Biol."},{"key":"4844_CR60","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","volume":"29","author":"A Dobin","year":"2013","unstructured":"Dobin, A. et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29, 15\u201321 (2013).","journal-title":"Bioinformatics"},{"key":"4844_CR61","doi-asserted-by":"publisher","first-page":"e108","DOI":"10.1093\/nar\/gkt214","volume":"41","author":"Y Liao","year":"2013","unstructured":"Liao, Y., Smyth, G. K. & Shi, W. The Subread aligner: fast, accurate and scalable read mapping by seed-and-vote. Nucleic Acids Res. 41, e108 (2013).","journal-title":"Nucleic Acids Res."},{"key":"4844_CR62","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1093\/bioinformatics\/btp616","volume":"26","author":"MD Robinson","year":"2010","unstructured":"Robinson, M. D., McCarthy, D. J. & Smyth, G. K. edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26, 139\u2013140 (2010).","journal-title":"Bioinformatics"},{"key":"4844_CR63","doi-asserted-by":"publisher","first-page":"e47","DOI":"10.1093\/nar\/gkv007","volume":"43","author":"ME Ritchie","year":"2015","unstructured":"Ritchie, M. E. et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 43, e47 (2015).","journal-title":"Nucleic Acids Res."},{"key":"4844_CR64","doi-asserted-by":"crossref","unstructured":"Martin, M. Cutadapt removes adapter sequences from high-throughput sequencing reads. EMBnet.journal 17, 10\u201312 (2011).","DOI":"10.14806\/ej.17.1.200"},{"key":"4844_CR65","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1093\/bioinformatics\/btt656","volume":"30","author":"Y Liao","year":"2014","unstructured":"Liao, Y., Smyth, G. K. & Shi, W. featureCounts: an efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics 30, 923\u2013930 (2014).","journal-title":"Bioinformatics"},{"key":"4844_CR66","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2014-15-2-r29","volume":"15","author":"CW Law","year":"2014","unstructured":"Law, C. W., Chen, Y., Shi, W. & Smyth, G. K. voom: precision weights unlock linear model analysis tools for RNA-seq read counts. Genome Biol. 15, R29 (2014).","journal-title":"Genome Biol."},{"key":"4844_CR67","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1089\/omi.2011.0118","volume":"16","author":"G Yu","year":"2012","unstructured":"Yu, G., Wang, L. G., Han, Y. & He, Q. Y. clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS 16, 284\u2013287 (2012).","journal-title":"OMICS"},{"key":"4844_CR68","doi-asserted-by":"publisher","first-page":"E5593","DOI":"10.1073\/pnas.1419161111","volume":"111","author":"S Shen","year":"2014","unstructured":"Shen, S. et al. rMATS: robust and flexible detection of differential alternative splicing from replicate RNA-seq data. Proc. Natl Acad. Sci. USA 111, E5593\u2013E5601 (2014).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"4844_CR69","unstructured":"Low, D. SPLINTER: splice interpreter of transcripts. R version 1.4.0 https:\/\/github.com\/dianalow\/SPLINTER\/ (2017)."},{"key":"4844_CR70","doi-asserted-by":"publisher","first-page":"3573","DOI":"10.1016\/j.cell.2021.04.048","volume":"184","author":"Y Hao","year":"2021","unstructured":"Hao, Y. et al. Integrated analysis of multimodal single-cell data. Cell 184, 3573\u20133587 (2021).","journal-title":"Cell"},{"key":"4844_CR71","doi-asserted-by":"publisher","first-page":"47","DOI":"10.12688\/f1000research.22139.1","volume":"9","author":"N Borcherding","year":"2020","unstructured":"Borcherding, N., Bormann, N. L. & Kraus, G. scRepertoire: an R-based toolkit for single-cell immune receptor analysis. F1000Res. 9, 47 (2020).","journal-title":"F1000Res."},{"key":"4844_CR72","doi-asserted-by":"publisher","first-page":"1247","DOI":"10.1158\/1535-7163.MCT-14-0913","volume":"14","author":"S Cuadrado-Castano","year":"2015","unstructured":"Cuadrado-Castano, S. et al. Enhancement of the proapoptotic properties of newcastle disease virus promotes tumor remission in syngeneic murine cancer models. Mol. Cancer Ther. 14, 1247\u20131258 (2015).","journal-title":"Mol. Cancer Ther."},{"key":"4844_CR73","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1111\/imr.12047","volume":"253","author":"NM Martinez","year":"2013","unstructured":"Martinez, N. M. & Lynch, K. W. Control of alternative splicing in immune responses: many regulators, many predictions, much still to learn. Immunol. Rev. 253, 216\u2013236 (2013).","journal-title":"Immunol. Rev."}],"updated-by":[{"DOI":"10.1038\/s41586-022-05184-0","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2022,8,9]],"date-time":"2022-08-09T00:00:00Z","timestamp":1660003200000}}],"container-title":["Nature"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41586-022-04844-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41586-022-04844-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41586-022-04844-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T14:03:12Z","timestamp":1777989792000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41586-022-04844-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,22]]},"references-count":73,"journal-issue":{"issue":"7916","published-print":{"date-parts":[[2022,6,30]]}},"alternative-id":["4844"],"URL":"https:\/\/doi.org\/10.1038\/s41586-022-04844-5","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-798338\/v1","asserted-by":"object"}]},"ISSN":["0028-0836","1476-4687"],"issn-type":[{"value":"0028-0836","type":"print"},{"value":"1476-4687","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,22]]},"assertion":[{"value":"9 August 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 May 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 June 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 August 2022","order":5,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":6,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A Correction to this paper has been published:","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"https:\/\/doi.org\/10.1038\/s41586-022-05184-0","URL":"https:\/\/doi.org\/10.1038\/s41586-022-05184-0","order":8,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"C.L. is the scientific director of the company NEMO Lab, and he served on a scientific advisory board for Mitsubishi Tanabe Pharma Europe, Cytokinetics, Neuraltus and Italfarmaco. The other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}