{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T08:26:54Z","timestamp":1770539214913,"version":"3.49.0"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,8,18]],"date-time":"2023-08-18T00:00:00Z","timestamp":1692316800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>During recent years, evidence has emerged that immune privileged sites such as the CNS and the retina may be more integrated in the systemic response to infection than was previously believed. In line with this, it was recently shown that a systemic acute virus infection leads to infiltration of CD8 T cells in the brains of immunocompetent mice. In this study, we extend these findings to the neurological tissue of the eye, namely the retina. We show that an acute systemic virus infection in mice leads to a transient CD8 T cell infiltration in the retina that is not directed by virus infection inside the retina. CD8 T cells were found throughout the retinal tissue, and had a high expression of CXCR6 and CXCR3, as also reported for tissue residing CD8 T cells in the lung and liver. We also show that the pigment epithelium lining the retina expresses CXCL16 (the ligand for CXCR6) similar to epithelial cells of the lung. Thus, our results suggest that the retina undergoes immune surveillance during a systemic infection, and that this surveillance appears to be directed by mechanisms similar to those described for non-privileged tissues.<\/jats:p>","DOI":"10.3389\/fimmu.2023.1221511","type":"journal-article","created":{"date-parts":[[2023,8,18]],"date-time":"2023-08-18T11:53:10Z","timestamp":1692359590000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Systemic virus infection results in CD8 T cell recruitment to the retina in the absence of local virus infection"],"prefix":"10.3389","volume":"14","author":[{"given":"Egle","family":"Paskeviciute","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heping","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bent","family":"Honor\u00e9","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henrik","family":"Vorum","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Torben Lykke","family":"S\u00f8rensen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan Pravsgaard","family":"Christensen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Allan Randrup","family":"Thomsen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mogens Holst","family":"Nissen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Abildgaard","family":"Steffensen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,8,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2012.00296","article-title":"The privileged immunity of immune privileged organs: the case of the eye","volume":"3","author":"Benhar","year":"2012","journal-title":"Front Immunol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2008.08.002","article-title":"Immune regulation and the eye","volume":"29","author":"Stein-Streilein","year":"2008","journal-title":"Trends Immunol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2012.00338","article-title":"Good news\u2013bad news: the Yin and Yang of immune privilege in the eye","volume":"3","author":"Forrester","year":"2012","journal-title":"Front Immunol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1007040","article-title":"Cytomegalovirus establishes a latent reservoir and triggers long-lasting inflammation in the eye","volume":"14","author":"Voigt","year":"2018","journal-title":"PloS Pathog"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-020-0711-8","article-title":"Peripherally induced brain tissue\u2013resident memory CD8+ T cells mediate protection against CNS infection","volume":"21","author":"Urban","year":"2020","journal-title":"Nat Immunol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00351","article-title":"Local antigen encounter is essential for establishing persistent CD8+ T-cell memory in the CNS","volume":"10","author":"Sch\u00f8ller","year":"2019","journal-title":"Front Immunol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1084\/jem.160.2.521","article-title":"Selection of genetic variants of lymphocytic choriomeningitis virus in spleens of persistently infected mice. Role in Suppression of Cytotoxic T Lymphocyte Response and Viral Persistence","volume":"160","author":"Ahmed","year":"1984","journal-title":"J Exp Med"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.8.4911-4927.2003","article-title":"Viral Persistence Alters CD8 T-Cell Immunodominance and Tissue Distribution and Results in Distinct Stages of Functional Impairment","volume":"77","author":"Wherry","year":"2003","journal-title":"J Virol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1167\/iovs.18-25721","article-title":"Chemokine expression in murine RPE\/choroid in response to systemic viral infection and elevated levels of circulating interferon-\u03b3","volume":"60","author":"Faber","year":"2019","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1096\/fj.03-1476fje","article-title":"A central role for inflammation in the pathogenesis of diabetic retinopathy","volume":"18","author":"Joussen","year":"2004","journal-title":"FASEB J"},{"key":"B11","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.pneurobio.2011.05.011","article-title":"Age related macular degeneration and drusen: Neuroinflammation in the retina","volume":"95","author":"Buschini","year":"2011","journal-title":"Prog Neurobiol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"724648","DOI":"10.1155\/2013\/724648","article-title":"Inflammation in retinal disease","volume":"2013","author":"Whitcup","year":"2013","journal-title":"Int J Inflam"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20181308","article-title":"CXCR6 regulates localization of tissue-resident memory CD8 T cells to the airways","volume":"216","author":"Wein","year":"2019","journal-title":"J Exp Med"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiu281","article-title":"The chemokine receptor CXCR6 Is required for the maintenance of liver memory CD8+ T cells specific for infectious pathogens","volume":"210","author":"Tse","year":"2014","journal-title":"J Infect Dis"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.1.277","article-title":"Role for CXCR6 in recruitment of activated CD8+ lymphocytes to inflamed liver","volume":"174","author":"Sato","year":"2005","journal-title":"J Immunol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.12-9963","article-title":"Chemokine expression in retinal pigment epithelial ARPE-19 cells in response to coculture with activated T cells","volume":"53","author":"Juel","year":"2012","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/0166-0934(91)90018-U","article-title":"Quantification of lymphocytic choriomeningitis virus with an immunological focus assay in 24- or 96-well plates","volume":"33","author":"Battegay","year":"1991","journal-title":"J Virol Methods"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.12-10385","article-title":"Complement factor H deficiency results in decreased neuroretinal expression of Cd59a in aged mice","volume":"53","author":"Faber","year":"2012","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxq061","article-title":"Innate and adaptive immune control of genetically engineered live-attenuated arenavirus vaccine prototypes","volume":"22","author":"Pinschewer","year":"2010","journal-title":"Int Immunol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.07-1522","article-title":"Characterization of a spontaneous mouse retinal pigment epithelial cell line B6-RPE07","volume":"49","author":"Chen","year":"2008","journal-title":"Investig Ophthalmol Vis Sci"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2011.01.003","article-title":"Retinal pigment epithelial cells upregulate expression of complement factors after co-culture with activated T cells","volume":"92","author":"Juel","year":"2011","journal-title":"Exp Eye Res"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1201682","article-title":"Cutting edge: intravascular staining redefines lung CD8 T cell responses","volume":"189","author":"Anderson","year":"2012","journal-title":"J Immunol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"eaaj1996","DOI":"10.1126\/sciimmunol.aaj1996","article-title":"Up-regulation of LFA-1 allows liver-resident memory T cells to patrol and remain in the hepatic sinusoids","volume":"2","author":"McNamara","year":"2017","journal-title":"Sci Immunol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1038\/79738","article-title":"A transmembrane CXC chemokine is a ligand for HIV-coreceptor Bonzo","volume":"1","author":"Matloubian","year":"2000","journal-title":"Nat Immunol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"43","DOI":"10.4049\/jimmunol.176.1.43","article-title":"The membrane-bound chemokine CXCL16 expressed on follicle-associated epithelium and M cells mediates lympho-epithelial interaction in GALT","volume":"176","author":"Hase","year":"2006","journal-title":"J Immunol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.4.1647","article-title":"Cutting edge: SR-PSOX\/CXC chemokine ligand 16 mediates bacterial phagocytosis by APCs through its chemokine domain","volume":"171","author":"Shimaoka","year":"2003","journal-title":"J Immunol"},{"key":"B27","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12974-014-0224-1","article-title":"Chemokine-mediated inflammation in the degenerating retina is coordinated by M\u00fcller cells, activated microglia, and retinal pigment epithelium","volume":"12","author":"Rutar","year":"2015","journal-title":"J Neuroinflammation"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13024-017-0175-y","article-title":"Microglia-derived IL-1\u03b2 promotes chemokine expression by M\u00fcller cells and RPE in focal retinal degeneration","volume":"12","author":"Natoli","year":"2017","journal-title":"Mol Neurodegener"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.7.4235","article-title":"CXCL10 is the key ligand for CXCR3 on CD8+ effector T cells involved in immune surveillance of the lymphocytic choriomeningitis virus-infected central nervous system","volume":"176","author":"Christensen","year":"2006","journal-title":"J Immunol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0123-04.2004","article-title":"Efficient T-cell surveillance of the CNS requires expression of the CXC chemokine receptor 3","volume":"24","author":"Christensen","year":"2004","journal-title":"J Neurosci"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01977","article-title":"Effector CD8 T cell-dependent zika virus control in the CNS: A matter of time and numbers","volume":"11","author":"Nazerai","year":"2020","journal-title":"Front Immunol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1221511\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,18]],"date-time":"2023-08-18T11:53:13Z","timestamp":1692359593000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1221511\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,18]]},"references-count":31,"alternative-id":["10.3389\/fimmu.2023.1221511"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2023.1221511","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,18]]},"article-number":"1221511"}}