PMID- 23878317
OWN - NLM
STAT- MEDLINE
DCOM- 20131106
LR  - 20211021
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 191
IP  - 5
DP  - 2013 Sep 1
TI  - Broadening the repertoire of functional herpes simplex virus type 1-specific CD8+ 
      T cells reduces viral reactivation from latency in sensory ganglia.
PG  - 2258-65
LID - 10.4049/jimmunol.1300585 [doi]
AB  - A large proportion of the world population harbors HSV type 1 (HSV-1) in a latent 
      state in their trigeminal ganglia (TG). TG-resident CD8(+) T cells appear 
      important for preventing HSV-1 reactivation from latency and recurrent herpetic 
      disease. In C57BL/6J mice, half of these cells are specific for an immunodominant 
      epitope on HSV-1 glycoprotein B, whereas the other half are specific for 18 
      subdominant epitopes. In this study, we show that the CD8(+) T cell dominance 
      hierarchy in the TG established during acute infection is maintained during 
      latency. However, CD8(+) T cells specific for subdominant epitopes lose 
      functionality, whereas those specific for the immunodominant epitope exhibit 
      increased functionality in latently infected TG. Furthermore, we show that IL-10 
      produced by 16.4 +/- 2.8% of TG-resident CD4(+) T cells maintains the 
      immunodominance hierarchy in part through selective inhibition of subdominant 
      CD8(+) T cell proliferation. Upon systemic anti-IL-10R Ab treatment, we observed 
      a significant expansion of functional subdominant CD8(+) T cells, resulting in 
      significantly improved protection from viral reactivation. In fact, systemic 
      anti-IL-10R Ab treatment prevented viral reactivation in up to 50% of treated 
      mice. Our results not only demonstrate that HSV-1 reactivation from latency can 
      be prevented by expanding the repertoire of functional TG-resident CD8(+) T 
      cells, but also that IL-10R blockade might have therapeutic potential to reduce 
      or eliminate recurrent herpetic disease.
FAU - St Leger, Anthony J
AU  - St Leger AJ
AD  - Department of Ophthalmology, University of Pittsburgh School of Medicine, 
      Pittsburgh, PA 15213, USA.
FAU - Jeon, Sohyun
AU  - Jeon S
FAU - Hendricks, Robert L
AU  - Hendricks RL
LA  - eng
GR  - P30 EY001792/EY/NEI NIH HHS/United States
GR  - R01 EY005945/EY/NEI NIH HHS/United States
GR  - R01-EY005945/EY/NEI NIH HHS/United States
GR  - P30-EY08098/EY/NEI NIH HHS/United States
GR  - R01 EY010359/EY/NEI NIH HHS/United States
GR  - T32-EY017271/EY/NEI NIH HHS/United States
GR  - T32 EY017271/EY/NEI NIH HHS/United States
GR  - P30 EY008098/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 - 20130722
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (Immunodominant Epitopes)
RN  - 130068-27-8 (Interleukin-10)
SB  - IM
MH  - Animals
MH  - CD4-Positive T-Lymphocytes/immunology/virology
MH  - CD8-Positive T-Lymphocytes/*immunology/virology
MH  - Disease Models, Animal
MH  - Epitopes, T-Lymphocyte/immunology
MH  - Female
MH  - Flow Cytometry
MH  - Ganglia, Sensory/immunology/*virology
MH  - Herpes Simplex/*immunology
MH  - Herpesvirus 1, Human/physiology
MH  - Immunodominant Epitopes/immunology
MH  - Interleukin-10/immunology
MH  - Lymphocyte Activation/immunology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Virus Activation/*immunology
MH  - Virus Latency/*immunology
PMC - PMC3779892
MID - NIHMS500094
EDAT- 2013/07/24 06:00
MHDA- 2013/11/07 06:00
PMCR- 2014/09/01
CRDT- 2013/07/24 06:00
PHST- 2013/07/24 06:00 [entrez]
PHST- 2013/07/24 06:00 [pubmed]
PHST- 2013/11/07 06:00 [medline]
PHST- 2014/09/01 00:00 [pmc-release]
AID - jimmunol.1300585 [pii]
AID - 10.4049/jimmunol.1300585 [doi]
PST - ppublish
SO  - J Immunol. 2013 Sep 1;191(5):2258-65. doi: 10.4049/jimmunol.1300585. Epub 2013 
      Jul 22.