PMID- 27171004
OWN - NLM
STAT- MEDLINE
DCOM- 20170710
LR  - 20210109
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 11
IP  - 5
DP  - 2016
TI  - Interferon Regulator Factor 8 (IRF8) Limits Ocular Pathology during HSV-1 
      Infection by Restraining the Activation and Expansion of CD8+ T Cells.
PG  - e0155420
LID - 10.1371/journal.pone.0155420 [doi]
LID - e0155420
AB  - Interferon Regulatory Factor-8 (IRF8) is constitutively expressed in monocytes 
      and B cell lineages and plays important roles in immunity to pathogens and 
      cancer. Although IRF8 expression is induced in activated T cells, the functional 
      relevance of IRF8 in T cell-mediated immunity is not well understood. In this 
      study, we used mice with targeted deletion of Irf8 in T-cells (IRF8KO) to 
      investigate the role of IRF8 in T cell-mediated responses during herpes simplex 
      virus 1 (HSV-1) infection of the eye. In contrast to wild type mice, 
      HSV-1-infected IRF8KO mice mounted a more robust anti-HSV-1 immune response, 
      which included marked expansion of HSV-1-specific CD8+ T cells, increased 
      infiltration of inflammatory cells into the cornea and trigeminal ganglia (TG) 
      and enhanced elimination of virus within the trigeminal ganglion. However, the 
      consequence of the enhanced immunological response was the development of ocular 
      inflammation, limbitis, and neutrophilic infiltration into the cornea of 
      HSV-1-infected IRF8KO mice. Surprisingly, we observed a marked increase in 
      virus-specific memory precursor effector cells (MPEC) in IRF8KO mice, suggesting 
      that IRF8 might play a role in regulating the differentiation of effector CD8+ T 
      cells to the memory phenotype. Together, our data suggest that IRF8 might play a 
      role in restraining excess lymphocyte proliferation. Thus, modulating IRF8 levels 
      in T cells can be exploited therapeutically to prevent immune-mediated ocular 
      pathology during autoimmune and infectious diseases of the eye.
FAU - Sun, Lin
AU  - Sun L
AD  - Molecular Immunology Section, National Eye Institute (NEI), National Institutes 
      of Health (NIH), Bethesda, Maryland, United States of America.
FAU - St Leger, Anthony J
AU  - St Leger AJ
AD  - Immunoregulation Section, NEI, NIH, Bethesda, Maryland, United States of America.
FAU - Yu, Cheng-Rong
AU  - Yu CR
AD  - Molecular Immunology Section, National Eye Institute (NEI), National Institutes 
      of Health (NIH), Bethesda, Maryland, United States of America.
FAU - He, Chang
AU  - He C
AD  - Molecular Immunology Section, National Eye Institute (NEI), National Institutes 
      of Health (NIH), Bethesda, Maryland, United States of America.
FAU - Mahdi, Rashid M
AU  - Mahdi RM
AD  - Molecular Immunology Section, National Eye Institute (NEI), National Institutes 
      of Health (NIH), Bethesda, Maryland, United States of America.
FAU - Chan, Chi-Chao
AU  - Chan CC
AD  - Immunopathology Section, NEI, NIH, Bethesda, Maryland, United States of America.
FAU - Wang, Hongsheng
AU  - Wang H
AD  - Laboratory of Immunogenetics, National Institute of Allergy and Infectious 
      Diseases (NIAID), NIH, Rockville, Maryland, United States of America.
FAU - Morse, Herbert C 3rd
AU  - Morse HC 3rd
AD  - Laboratory of Immunogenetics, National Institute of Allergy and Infectious 
      Diseases (NIAID), NIH, Rockville, Maryland, United States of America.
FAU - Egwuagu, Charles E
AU  - Egwuagu CE
AD  - Molecular Immunology Section, National Eye Institute (NEI), National Institutes 
      of Health (NIH), Bethesda, Maryland, United States of America.
LA  - eng
GR  - Z01 EY000350/ImNIH/Intramural NIH HHS/United States
GR  - Z01 EY000372/ImNIH/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20160512
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Antigens, Viral)
RN  - 0 (Integrins)
RN  - 0 (Interferon Regulatory Factors)
RN  - 0 (Receptors, Chemokine)
RN  - 0 (interferon regulatory factor-8)
SB  - IM
MH  - Adoptive Transfer
MH  - Animals
MH  - Antigens, Viral/immunology
MH  - CD8-Positive T-Lymphocytes/immunology/*pathology
MH  - Cell Proliferation
MH  - Eye/*pathology/*virology
MH  - Herpes Simplex/*immunology/*virology
MH  - Herpesvirus 1, Human/*physiology
MH  - Immunologic Memory
MH  - Inflammation/complications/immunology/pathology
MH  - Integrins/metabolism
MH  - Interferon Regulatory Factors/*metabolism
MH  - Lymphocyte Activation/*immunology
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Phenotype
MH  - Receptors, Chemokine/metabolism
MH  - Viral Load
PMC - PMC4865128
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2016/05/14 06:00
MHDA- 2017/07/14 06:00
PMCR- 2016/05/12
CRDT- 2016/05/13 06:00
PHST- 2015/09/01 00:00 [received]
PHST- 2016/04/28 00:00 [accepted]
PHST- 2016/05/13 06:00 [entrez]
PHST- 2016/05/14 06:00 [pubmed]
PHST- 2017/07/14 06:00 [medline]
PHST- 2016/05/12 00:00 [pmc-release]
AID - PONE-D-15-38057 [pii]
AID - 10.1371/journal.pone.0155420 [doi]
PST - epublish
SO  - PLoS One. 2016 May 12;11(5):e0155420. doi: 10.1371/journal.pone.0155420. 
      eCollection 2016.