{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T06:52:14Z","timestamp":1778223134766,"version":"3.51.4"},"reference-count":46,"publisher":"American Society for Microbiology","issue":"13","license":[{"start":{"date-parts":[[2011,7,1]],"date-time":"2011-07-01T00:00:00Z","timestamp":1309478400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2011,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Interleukin-10 (IL-10) mRNA is rapidly upregulated in the central nervous system (CNS) following infection with neurotropic coronavirus and remains elevated during persistent infection. Infection of transgenic IL-10\/green fluorescent protein (GFP) reporter mice revealed that CNS-infiltrating T cells were the major source of IL-10, with minimal IL-10 production by macrophages and resident microglia. The proportions of IL-10-producing cells were initially similar in CD8<jats:sup>+<\/jats:sup>and CD4<jats:sup>+<\/jats:sup>T cells but diminished rapidly in CD8<jats:sup>+<\/jats:sup>T cells as the virus was controlled. Overall, the majority of IL-10-producing CD8<jats:sup>+<\/jats:sup>T cells were specific for the immunodominant major histocompatibility complex (MHC) class I epitope. Unlike CD8<jats:sup>+<\/jats:sup>T cells, a large proportion of CD4<jats:sup>+<\/jats:sup>T cells within the CNS retained IL-10 production throughout persistence. Furthermore, elevated frequencies of IL-10-producing CD4<jats:sup>+<\/jats:sup>T cells in the spinal cord supported preferential maintenance of IL-10 production at the site of viral persistence and tissue damage. IL-10 was produced primarily by the CD25<jats:sup>+<\/jats:sup>CD4<jats:sup>+<\/jats:sup>T cell subset during acute infection but prevailed in CD25<jats:sup>\u2212<\/jats:sup>CD4<jats:sup>+<\/jats:sup>T cells during the transition to persistent infection and thereafter. Overall, these data demonstrate significant fluidity in the T-cell-mediated IL-10 response during viral encephalitis and persistence. While IL-10 production by CD8<jats:sup>+<\/jats:sup>T cells was limited primarily to the time of acute effector function, CD4<jats:sup>+<\/jats:sup>T cells continued to produce IL-10 throughout infection. Moreover, a shift from predominant IL-10 production by CD25<jats:sup>+<\/jats:sup>CD4<jats:sup>+<\/jats:sup>T cells to CD25<jats:sup>\u2212<\/jats:sup>CD4<jats:sup>+<\/jats:sup>T cells suggests that a transition to nonclassical regulatory T cells precedes and is retained during CNS viral persistence.<\/jats:p>","DOI":"10.1128\/jvi.00200-11","type":"journal-article","created":{"date-parts":[[2011,4,28]],"date-time":"2011-04-28T02:57:00Z","timestamp":1303959420000},"page":"6702-6713","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":37,"title":["Shifting Hierarchies of Interleukin-10-Producing T Cell Populations in the Central Nervous System during Acute and Persistent Viral Encephalomyelitis"],"prefix":"10.1128","volume":"85","author":[{"given":"Shweta S.","family":"Puntambekar","sequence":"first","affiliation":[{"name":"Department of Neurosciences, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cornelia C.","family":"Bergmann","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carine","family":"Savarin","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher L.","family":"Karp","sequence":"additional","affiliation":[{"name":"Division of Molecular Immunology, Cincinnati Children's Hospital Research Foundation, Cincinnati, Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy W.","family":"Phares","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriel I.","family":"Parra","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David R.","family":"Hinton","sequence":"additional","affiliation":[{"name":"Department of Pathology, The University of Southern California Keck School of Medicine, Los Angeles, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen A.","family":"Stohlman","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2008.12.014"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.5.2752"},{"key":"e_1_3_2_4_2","doi-asserted-by":"crossref","first-page":"3379","DOI":"10.4049\/jimmunol.163.6.3379","article-title":"Inverted immunodominance and impaired cytolytic function of cytolytic CD8+ T cells during viral persistence in the central nervous system","volume":"163","author":"Bergmann C. C.","year":"1999","unstructured":"BergmannC. C. AltmanJ. D. HintonD. StohlmanS. A.. 1999. Inverted immunodominance and impaired cytolytic function of cytolytic CD8+ T cells during viral persistence in the central nervous system. J. Immunol. 163:3379\u20133387.","journal-title":"J. Immunol."},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-77-2-315"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1343"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.4.1739-1750.2004"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1679"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2007.02.006"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0811139106"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1492"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.69.12.8127-8131.1995"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0609406"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.9.5771"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20061462"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2010.03.004"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1760"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.2272"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1540"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.58.3.869-875.1986"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.75.6.3043-3047.2001"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01794-07"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1207-1281"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1001535"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00315-09"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1615\/CritRevImmunol.v30.i2.20"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1998.9170"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0900185"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.4.2775-2778.2003"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.19.1.683"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri2097"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1997.8613"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2567.2001.01286.x"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2009.11.003"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1001984"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01267-08"},{"key":"e_1_3_2_37_2","doi-asserted-by":"crossref","first-page":"5320","DOI":"10.4049\/jimmunol.160.11.5320","article-title":"Central nervous system microglial activation and proliferation follows direct interaction with tissue infiltrating T cell blasts","volume":"160","author":"Sedgwick J. D.","year":"1998","unstructured":"SedgwickJ. D. FordA. L. FoulcherE. AirriessR.. 1998. Central nervous system microglial activation and proliferation follows direct interaction with tissue infiltrating T cell blasts. J. Immunol. 160:5320\u20135330.","journal-title":"J. Immunol."},{"key":"e_1_3_2_38_2","doi-asserted-by":"crossref","first-page":"2713","DOI":"10.4049\/jimmunol.147.8.2713","article-title":"Production of IL-10 by CD4+ T lymphocytes correlates with down-regulation of Th1 cytokine synthesis in helminth infection","volume":"147","author":"Sher A.","year":"1991","unstructured":"SherA. FiorentinoD. CasparP. PearceE. MosmannT.. 1991. Production of IL-10 by CD4+ T lymphocytes correlates with down-regulation of Th1 cytokine synthesis in helminth infection. J. Immunol. 147:2713\u20132716.","journal-title":"J. Immunol."},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/43454"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.1929"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0903918"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1003292"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200535123"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.1.371"},{"key":"e_1_3_2_45_2","first-page":"744","article-title":"Sequential infection of glial cells by the murine hepatitis virus JHM strain (MHV-4) leads to a characteristic distribution of demyelination","volume":"66","author":"Wang F. I.","year":"1992","unstructured":"WangF. I. HintonD. R. GilmoreW. TrousdaleM. D. FlemingJ. O.. 1992. Sequential infection of glial cells by the murine hepatitis virus JHM strain (MHV-4) leads to a characteristic distribution of demyelination. Lab. Invest. 66:744\u2013754.","journal-title":"Lab. Invest."},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.4.2278"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2006.01.027"}],"container-title":["Journal of Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.00200-11","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.00200-11","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,6]],"date-time":"2023-06-06T14:10:08Z","timestamp":1686060608000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/JVI.00200-11"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,7]]},"references-count":46,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2011,7]]}},"alternative-id":["10.1128\/JVI.00200-11"],"URL":"https:\/\/doi.org\/10.1128\/jvi.00200-11","relation":{},"ISSN":["0022-538X","1098-5514"],"issn-type":[{"value":"0022-538X","type":"print"},{"value":"1098-5514","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,7]]},"assertion":[{"value":"2011-01-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2011-04-18","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2011-06-09","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}