{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T22:30:06Z","timestamp":1791412206310,"version":"4.3.3"},"reference-count":67,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2017,7,1]],"date-time":"2017-07-01T00:00:00Z","timestamp":1498867200000},"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":[[2017,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>HSV type 1 (HSV-1) is a prevalent human pathogen that infects &amp;gt;3.72 billion individuals worldwide and can cause potentially blinding recurrent corneal herpetic disease. HSV-1 establishes latency within sensory neurons of trigeminal ganglia (TG), and TG-resident CD8+ T cells play a critical role in preventing its reactivation. The repertoire, phenotype, and function of protective CD8+ T cells are unknown. Bolstering the apparent feeble numbers of CD8+ T cells in TG remains a challenge for immunotherapeutic strategies. In this study, a comprehensive panel of 467 HLA-A*0201\u2013restricted CD8+ T cell epitopes was predicted from the entire HSV-1 genome. CD8+ T cell responses to these genome-wide epitopes were compared in HSV-1\u2013seropositive symptomatic individuals (with a history of numerous episodes of recurrent herpetic disease) and asymptomatic (ASYMP) individuals (who are infected but never experienced any recurrent herpetic disease). Frequent polyfunctional HSV-specific IFN-\u03b3+CD107a\/b+CD44highCD62LlowCD8+ effector memory T cells were detected in ASYMP individuals and were primarily directed against three \u201cASYMP\u201d epitopes. In contrast, symptomatic individuals have more monofunctional CD44highCD62LhighCD8+ central memory T cells. Furthermore, therapeutic immunization with an innovative prime\/pull vaccine, based on priming with multiple ASYMP epitopes (prime) and neurotropic TG delivery of the T cell\u2013attracting chemokine CXCL10 (pull), boosted the number and function of CD44highCD62LlowCD8+ effector memory T cells and CD103highCD8+ tissue-resident T cells in TG of latently infected HLA-A*0201\u2013transgenic mice and reduced recurrent ocular herpes following UV-B\u2013induced reactivation. These findings have profound implications in the development of T cell\u2013based immunotherapeutic strategies to treat blinding recurrent herpes infection and disease.<\/jats:p>","DOI":"10.4049\/jimmunol.1700145","type":"journal-article","created":{"date-parts":[[2017,5,25]],"date-time":"2017-05-25T00:40:23Z","timestamp":1495672823000},"page":"186-203","source":"Crossref","is-referenced-by-count":46,"title":["Bolstering the Number and Function of HSV-1\u2013Specific CD8+ Effector Memory T Cells and Tissue-Resident Memory T Cells in Latently Infected Trigeminal Ganglia Reduces Recurrent Ocular Herpes Infection and Disease"],"prefix":"10.1093","volume":"199","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0751-0930","authenticated-orcid":false,"given":"Arif A","family":"Khan","sequence":"first","affiliation":[{"name":"Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California, Irvine, School of Medicine , Irvine, CA 92697"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruchi","family":"Srivastava","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California, Irvine, School of Medicine , Irvine, CA 92697"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5410-2593","authenticated-orcid":false,"given":"Aziz A","family":"Chentoufi","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California, Irvine, School of Medicine , Irvine, CA 92697"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Kritzer","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California, Irvine, School of Medicine , Irvine, CA 92697"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5234-0769","authenticated-orcid":false,"given":"Sravya","family":"Chilukuri","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California, Irvine, School of Medicine , Irvine, CA 92697"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumit","family":"Garg","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California, Irvine, School of Medicine , Irvine, CA 92697"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David C","family":"Yu","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California, Irvine, School of Medicine , Irvine, CA 92697"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hawa","family":"Vahed","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California, Irvine, School of Medicine , Irvine, CA 92697"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Huang","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California, Irvine, School of Medicine , Irvine, CA 92697"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina A","family":"Syed","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California, Irvine, School of Medicine , Irvine, CA 92697"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie N","family":"Furness","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California, Irvine, School of Medicine , Irvine, CA 92697"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tien T","family":"Tran","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California, Irvine, School of Medicine , Irvine, CA 92697"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nesburn B","family":"Anthony","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California, Irvine, School of Medicine , Irvine, CA 92697"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine E","family":"McLaren","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, University of California , Irvine, Irvine, CA 92697"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Sidney","sequence":"additional","affiliation":[{"name":"Department of Vaccine Discovery, La Jolla Institute for Allergy and Immunology , La Jolla, CA 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7013-2250","authenticated-orcid":false,"given":"Alessandro","family":"Sette","sequence":"additional","affiliation":[{"name":"Department of Vaccine Discovery, La Jolla Institute for Allergy and Immunology , La Jolla, CA 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randolph J","family":"Noelle","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth , Lebanon, NH 03755"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lbachir","family":"BenMohamed","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California, Irvine, School of Medicine , Irvine, CA 92697"},{"name":"Department of Molecular Biology and Biochemistry, University of California, Irvine, School of Medicine , Irvine, CA 92697"},{"name":"Institute for Immunology, University of California, Irvine, School of Medicine , Irvine, CA 92697"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,7,1]]},"reference":[{"key":"2025030612104415000_r1","doi-asserted-by":"crossref","first-page":"e01793-16","DOI":"10.1128\/JVI.01793-16","article-title":"Human asymptomatic epitopes identified from the herpes simplex virus tegument protein VP13\/14 (UL47) preferentially recall polyfunctional effector memory CD44high CD62Llow CD8+ TEM cells and protect humanized HLA-A*02:01 transgenic mice against ocular herpesvirus infection","volume":"91","author":"Srivastava","year":"2017","journal-title":"J. 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Sci."},{"key":"2025030612104415000_r33","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1189\/jlb.0904486","article-title":"Elucidating the protective and pathologic T cell species in the virus-induced corneal immunoinflammatory condition herpetic stromal keratitis","volume":"77","author":"Banerjee","year":"2005","journal-title":"J. Leukoc. Biol."},{"key":"2025030612104415000_r34","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/2042-4280-2-5","article-title":"Circulating herpes simplex type 1 (HSV-1)-specific CD8+ T cells do not access HSV-1 latently infected trigeminal ganglia","volume":"2","author":"Himmelein","year":"2011","journal-title":"Herpesviridae"},{"key":"2025030612104415000_r35","first-page":"Unit 18.13","article-title":"Measurement of MHC\/peptide interactions by gel filtration or monoclonal antibody capture","volume":"Chapter 18","author":"Sidney","year":"2013","journal-title":"Curr. Protoc. 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