PMID- 28539429 OWN - NLM STAT- MEDLINE DCOM- 20170927 LR - 20220318 IS - 1550-6606 (Electronic) IS - 0022-1767 (Print) IS - 0022-1767 (Linking) VI - 199 IP - 1 DP - 2017 Jul 1 TI - Bolstering the Number and Function of HSV-1-Specific CD8(+) Effector Memory T Cells and Tissue-Resident Memory T Cells in Latently Infected Trigeminal Ganglia Reduces Recurrent Ocular Herpes Infection and Disease. PG - 186-203 LID - 10.4049/jimmunol.1700145 [doi] AB - HSV type 1 (HSV-1) is a prevalent human pathogen that infects >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-restricted 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-seropositive 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-gamma(+)CD107(a/b+)CD44(high)CD62L(low)CD8(+) effector memory T cells were detected in ASYMP individuals and were primarily directed against three "ASYMP" epitopes. In contrast, symptomatic individuals have more monofunctional CD44(high)CD62L(high)CD8(+) 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-attracting chemokine CXCL10 (pull), boosted the number and function of CD44(high)CD62L(low)CD8(+) effector memory T cells and CD103(high)CD8(+) tissue-resident T cells in TG of latently infected HLA-A*0201-transgenic mice and reduced recurrent ocular herpes following UV-B-induced reactivation. These findings have profound implications in the development of T cell-based immunotherapeutic strategies to treat blinding recurrent herpes infection and disease. CI - Copyright (c) 2017 by The American Association of Immunologists, Inc. FAU - Khan, Arif A AU - Khan AA AUID- ORCID: 0000-0002-0751-0930 AD - Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California, Irvine, School of Medicine, Irvine, CA 92697. FAU - Srivastava, Ruchi AU - Srivastava R AD - Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California, Irvine, School of Medicine, Irvine, CA 92697. FAU - Chentoufi, Aziz A AU - Chentoufi AA AUID- ORCID: 0000-0002-5410-2593 AD - Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California, Irvine, School of Medicine, Irvine, CA 92697. FAU - Kritzer, Elizabeth AU - Kritzer E AD - Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California, Irvine, School of Medicine, Irvine, CA 92697. FAU - Chilukuri, Sravya AU - Chilukuri S AUID- ORCID: 0000-0001-5234-0769 AD - Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California, Irvine, School of Medicine, Irvine, CA 92697. FAU - Garg, Sumit AU - Garg S AD - Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California, Irvine, School of Medicine, Irvine, CA 92697. FAU - Yu, David C AU - Yu DC AD - Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California, Irvine, School of Medicine, Irvine, CA 92697. FAU - Vahed, Hawa AU - Vahed H AD - Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California, Irvine, School of Medicine, Irvine, CA 92697. FAU - Huang, Lei AU - Huang L AD - Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California, Irvine, School of Medicine, Irvine, CA 92697. FAU - Syed, Sabrina A AU - Syed SA AD - Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California, Irvine, School of Medicine, Irvine, CA 92697. FAU - Furness, Julie N AU - Furness JN AD - Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California, Irvine, School of Medicine, Irvine, CA 92697. FAU - Tran, Tien T AU - Tran TT AD - Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California, Irvine, School of Medicine, Irvine, CA 92697. FAU - Anthony, Nesburn B AU - Anthony NB AD - Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California, Irvine, School of Medicine, Irvine, CA 92697. FAU - McLaren, Christine E AU - McLaren CE AD - Department of Epidemiology, University of California, Irvine, Irvine, CA 92697. FAU - Sidney, John AU - Sidney J AD - Department of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037. FAU - Sette, Alessandro AU - Sette A AUID- ORCID: 0000-0001-7013-2250 AD - Department of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037. FAU - Noelle, Randolph J AU - Noelle RJ AD - Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, NH 03755. FAU - BenMohamed, Lbachir AU - BenMohamed L AD - Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California, Irvine, School of Medicine, Irvine, CA 92697; Lbenmoha@uci.edu. AD - Department of Molecular Biology and Biochemistry, University of California, Irvine, School of Medicine, Irvine, CA 92697; and. AD - Institute for Immunology, University of California, Irvine, School of Medicine, Irvine, CA 92697. LA - eng GR - R01 EY026103/EY/NEI NIH HHS/United States GR - R01 EY019896/EY/NEI NIH HHS/United States GR - R21 AI110902/AI/NIAID NIH HHS/United States GR - UL1 TR001414/TR/NCATS NIH HHS/United States GR - P30 CA062203/CA/NCI NIH HHS/United States GR - R01 EY014900/EY/NEI NIH HHS/United States GR - R01 EY024618/EY/NEI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20170524 PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Chemokine CXCL10) RN - 0 (Cxcl10 protein, mouse) RN - 0 (Epitopes) RN - 0 (Epitopes, T-Lymphocyte) SB - IM MH - Adult MH - Aged MH - Animals MH - CD8-Positive T-Lymphocytes/*immunology/physiology MH - Chemokine CXCL10/immunology MH - Epitopes/chemistry/immunology/isolation & purification MH - Epitopes, T-Lymphocyte/immunology MH - Female MH - Herpesvirus 1, Human/*immunology MH - Humans MH - Immunization MH - *Immunologic Memory MH - Keratitis, Herpetic/*immunology/therapy/virology MH - Male MH - Mice MH - Mice, Transgenic MH - Middle Aged MH - Recurrence MH - Trigeminal Ganglion/cytology/*immunology/*virology MH - *Virus Latency MH - Young Adult PMC - PMC5515716 MID - NIHMS872169 COIS- Conflict of interest: The authors have declared that no conflict of interest exists EDAT- 2017/05/26 06:00 MHDA- 2017/09/28 06:00 PMCR- 2018/07/01 CRDT- 2017/05/26 06:00 PHST- 2017/01/27 00:00 [received] PHST- 2017/04/21 00:00 [accepted] PHST- 2017/05/26 06:00 [pubmed] PHST- 2017/09/28 06:00 [medline] PHST- 2017/05/26 06:00 [entrez] PHST- 2018/07/01 00:00 [pmc-release] AID - jimmunol.1700145 [pii] AID - 10.4049/jimmunol.1700145 [doi] PST - ppublish SO - J Immunol. 2017 Jul 1;199(1):186-203. doi: 10.4049/jimmunol.1700145. Epub 2017 May 24.