PMID- 29875235
OWN - NLM
STAT- MEDLINE
DCOM- 20180817
LR  - 20190131
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 92
IP  - 16
DP  - 2018 Aug 15
TI  - Batf3-Dependent Dendritic Cells Promote Optimal CD8 T Cell Responses against 
      Respiratory Poxvirus Infection.
LID - 10.1128/JVI.00495-18 [doi]
LID - e00495-18
AB  - Respiratory infection with vaccinia virus (VacV) elicits robust CD8(+) T cell 
      responses that play an important role in host resistance. In the lung, VacV 
      encounters multiple tissue-resident antigen-presenting cell (APC) populations, 
      but which cell plays a dominant role in priming of virus-specific CD8(+) effector 
      T cell responses remains poorly defined. We used Batf3(-/-) mice to investigate 
      the impact of CD103(+) and CD8alpha(+) dendritic cell (DC) deficiency on anti-VacV 
      CD8(+) T cell responses. We found that Batf3(-/-) mice were more susceptible to 
      VacV infection, exhibiting profound weight loss, which correlated with impaired 
      accumulation of gamma interferon (IFN-gamma)-producing CD8(+) T cells in the lungs. 
      This was largely due to defective priming since early in the response, 
      antigen-specific CD8(+) T cells in the draining lymph nodes of Batf3(-/-) mice 
      expressed significantly reduced levels of Ki67, CD25, and T-bet. These results 
      underscore a specific role for Batf3-dependent DCs in regulating priming and 
      expansion of effector CD8(+) T cells necessary for host resistance against acute 
      respiratory VacV infection.IMPORTANCE During respiratory infection with vaccinia 
      virus (VacV), a member of Poxviridae family, CD8(+) T cells play important role 
      in resolving the primary infection. Effector CD8(+) T cells clear the virus by 
      accumulating in the infected lungs in large numbers and secreting molecules such 
      as IFN-gamma that kill virally infected cells. However, precise cell types that 
      regulate the generation of effector CD8(+) T cells in the lungs are not well 
      defined. Dendritic cells (DCs) are a heterogeneous population of immune cells 
      that are recognized as key initiators and regulators of T-cell-mediated immunity. 
      In this study, we reveal that a specific subset of DCs that are dependent on the 
      transcription factor Batf3 for their development regulate the magnitude of CD8(+) 
      T cell effector responses in the lungs, thereby providing protection during 
      pulmonary VacV infection.
CI  - Copyright (c) 2018 American Society for Microbiology.
FAU - Desai, Pritesh
AU  - Desai P
AD  - Department of Pathology, Immunology & Laboratory Medicine, University of Florida, 
      Gainesville, Florida, USA.
FAU - Tahiliani, Vikas
AU  - Tahiliani V
AD  - Department of Pathology, Immunology & Laboratory Medicine, University of Florida, 
      Gainesville, Florida, USA.
FAU - Abboud, Georges
AU  - Abboud G
AD  - Department of Pathology, Immunology & Laboratory Medicine, University of Florida, 
      Gainesville, Florida, USA.
FAU - Stanfield, Jessica
AU  - Stanfield J
AD  - Department of Pathology, Immunology & Laboratory Medicine, University of Florida, 
      Gainesville, Florida, USA.
FAU - Salek-Ardakani, Shahram
AU  - Salek-Ardakani S
AD  - Department of Pathology, Immunology & Laboratory Medicine, University of Florida, 
      Gainesville, Florida, USA ssalek@ufl.edu.
LA  - eng
GR  - R01 AI087734/AI/NIAID NIH HHS/United States
GR  - R21 AI077079/AI/NIAID NIH HHS/United States
GR  - T32 AR007603/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20180731
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Antigens, CD)
RN  - 0 (Basic-Leucine Zipper Transcription Factors)
RN  - 0 (CD8 Antigens)
RN  - 0 (CD8 antigen, alpha chain)
RN  - 0 (Integrin alpha Chains)
RN  - 0 (Repressor Proteins)
RN  - 0 (SNFT protein, mouse)
RN  - 0 (alpha E integrins)
SB  - IM
MH  - Animals
MH  - Antigens, CD/analysis
MH  - Basic-Leucine Zipper Transcription Factors/*analysis/deficiency
MH  - CD8 Antigens/analysis
MH  - CD8-Positive T-Lymphocytes/*immunology
MH  - Dendritic Cells/*chemistry/*immunology
MH  - Integrin alpha Chains/analysis
MH  - Mice
MH  - Mice, Knockout
MH  - Poxviridae Infections/*immunology
MH  - Repressor Proteins/*analysis/deficiency
MH  - Respiratory Tract Infections/*immunology
MH  - Vaccinia virus/*immunology
PMC - PMC6069197
OTO - NOTNLM
OT  - CD8 T cells
OT  - dendritic cells
OT  - effector functions
OT  - lung
OT  - lung infection
OT  - poxvirus
OT  - respiratory
OT  - vaccinia
OT  - vaccinia virus
EDAT- 2018/06/08 06:00
MHDA- 2018/08/18 06:00
PMCR- 2019/01/31
CRDT- 2018/06/08 06:00
PHST- 2018/03/23 00:00 [received]
PHST- 2018/05/23 00:00 [accepted]
PHST- 2018/06/08 06:00 [pubmed]
PHST- 2018/08/18 06:00 [medline]
PHST- 2018/06/08 06:00 [entrez]
PHST- 2019/01/31 00:00 [pmc-release]
AID - JVI.00495-18 [pii]
AID - 00495-18 [pii]
AID - 10.1128/JVI.00495-18 [doi]
PST - epublish
SO  - J Virol. 2018 Jul 31;92(16):e00495-18. doi: 10.1128/JVI.00495-18. Print 2018 Aug 
      15.