التفاصيل البيبلوغرافية
| العنوان: |
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 |
| المؤلفون: |
Khan, Arif A, Srivastava, Ruchi, Chentoufi, Aziz A, Kritzer, Elizabeth, Chilukuri, Sravya, Garg, Sumit, Yu, David C, Vahed, Hawa, Huang, Lei, Syed, Sabrina A, Furness, Julie N, Tran, Tien T, Anthony, Nesburn B, McLaren, Christine E, Sidney, John, Sette, Alessandro, Noelle, Randolph J, BenMohamed, Lbachir |
| المصدر: |
The Journal of Immunology, vol 199, iss 1 |
| بيانات النشر: |
eScholarship, University of California |
| سنة النشر: |
2017 |
| المجموعة: |
University of California: eScholarship |
| مصطلحات موضوعية: |
Immunization, Neurosciences, Vaccine Related, Sexually Transmitted Infections, Infectious Diseases, Aetiology, 2.1 Biological and endogenous factors, Infection, Good Health and Well Being, Adult, Aged, Animals, CD8-Positive T-Lymphocytes, Chemokine CXCL10, Epitopes, T-Lymphocyte, Female, Herpesvirus 1, Human, Humans, Immunologic Memory, Keratitis, Herpetic, Male, Mice, Transgenic, Middle Aged, Recurrence, Trigeminal Ganglion, Virus Latency |
| جغرافية الموضوع: |
186 - 203 |
| الوصف: |
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-γ+CD107a/b+CD44highCD62LlowCD8+ effector memory T cells were detected in ASYMP individuals and were primarily directed against three "ASYMP" 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-attracting 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-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. |
| نوع الوثيقة: |
article in journal/newspaper |
| وصف الملف: |
application/pdf |
| اللغة: |
unknown |
| العلاقة: |
qt6kd968h5; https://escholarship.org/uc/item/6kd968h5Test |
| الإتاحة: |
https://escholarship.org/uc/item/6kd968h5Test |
| حقوق: |
public |
| رقم الانضمام: |
edsbas.D31E8564 |
| قاعدة البيانات: |
BASE |
