PMID- 32125285
OWN - NLM
STAT- MEDLINE
DCOM- 20210202
LR  - 20240411
IS  - 1558-8238 (Electronic)
IS  - 0021-9738 (Print)
IS  - 0021-9738 (Linking)
VI  - 130
IP  - 6
DP  - 2020 Jun 1
TI  - Tissue-resident T cell-derived cytokines eliminate herpes simplex 
      virus-2-infected cells.
PG  - 2903-2919
LID - 132583 [pii]
LID - 10.1172/JCI132583 [doi]
AB  - The mechanisms underlying rapid elimination of herpes simplex virus-2 (HSV-2) in 
      the human genital tract despite low CD8+ and CD4+ tissue-resident T cell (Trm 
      cell) density are unknown. We analyzed shedding episodes during chronic HSV-2 
      infection; viral clearance always predominated within 24 hours of detection even 
      when viral load exceeded 1 x 107 HSV DNA copies, and surges in granzyme B and 
      IFN-gamma occurred within the early hours after reactivation and correlated with 
      local viral load. We next developed an agent-based mathematical model of an HSV-2 
      genital ulcer to integrate mechanistic observations of Trm cells in in situ 
      proliferation, trafficking, cytolytic effects, and cytokine alarm signaling from 
      murine studies with viral kinetics, histopathology, and lesion size data from 
      humans. A sufficiently high density of HSV-2-specific Trm cells predicted rapid 
      elimination of infected cells, but our data suggest that such Trm cell densities 
      are relatively uncommon in infected tissues. At lower, more commonly observed Trm 
      cell densities, Trm cells must initiate a rapidly diffusing, polyfunctional 
      cytokine response with activation of bystander T cells in order to eliminate a 
      majority of infected cells and eradicate briskly spreading HSV-2 infection.
FAU - Roychoudhury, Pavitra
AU  - Roychoudhury P
AD  - Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 
      Seattle, Washington, USA.
AD  - Department of Laboratory Medicine and.
FAU - Swan, David A
AU  - Swan DA
AD  - Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 
      Seattle, Washington, USA.
FAU - Duke, Elizabeth
AU  - Duke E
AD  - Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 
      Seattle, Washington, USA.
AD  - Department of Medicine, University of Washington, Seattle, Washington, USA.
FAU - Corey, Lawrence
AU  - Corey L
AD  - Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 
      Seattle, Washington, USA.
AD  - Department of Laboratory Medicine and.
AD  - Department of Medicine, University of Washington, Seattle, Washington, USA.
AD  - Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, 
      Washington, USA.
FAU - Zhu, Jia
AU  - Zhu J
AD  - Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 
      Seattle, Washington, USA.
AD  - Department of Laboratory Medicine and.
FAU - Dave, Veronica
AU  - Dave V
AD  - Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 
      Seattle, Washington, USA.
AD  - Department of Global Health and.
FAU - Spuhler, Laura Richert
AU  - Spuhler LR
AD  - Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 
      Seattle, Washington, USA.
FAU - Lund, Jennifer M
AU  - Lund JM
AD  - Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 
      Seattle, Washington, USA.
AD  - Department of Global Health and.
FAU - Prlic, Martin
AU  - Prlic M
AD  - Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 
      Seattle, Washington, USA.
AD  - Department of Global Health and.
AD  - Department of Immunology, University of Washington, Seattle, Washington, USA.
FAU - Schiffer, Joshua T
AU  - Schiffer JT
AD  - Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 
      Seattle, Washington, USA.
AD  - Department of Medicine, University of Washington, Seattle, Washington, USA.
AD  - Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, 
      Washington, USA.
LA  - eng
GR  - T32 AI007509/AI/NIAID NIH HHS/United States
GR  - R01 AI111780/AI/NIAID NIH HHS/United States
GR  - R01 AI121129/AI/NIAID NIH HHS/United States
GR  - R01 AI134878/AI/NIAID NIH HHS/United States
GR  - P01 AI030731/AI/NIAID NIH HHS/United States
GR  - KL2 TR002317/TR/NCATS NIH HHS/United States
GR  - P30 AI027757/AI/NIAID NIH HHS/United States
GR  - R01 AI143773/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - J Clin Invest
JT  - The Journal of clinical investigation
JID - 7802877
RN  - 0 (Cytokines)
SB  - IM
MH  - Animals
MH  - CD4-Positive T-Lymphocytes/*immunology/pathology
MH  - CD8-Positive T-Lymphocytes/*immunology/pathology
MH  - Chronic Disease
MH  - Cytokines/*immunology
MH  - Herpes Genitalis/*immunology/pathology
MH  - Herpesvirus 2, Human/*immunology
MH  - Humans
MH  - *Immunologic Memory
MH  - Mice
PMC - PMC7260013
OTO - NOTNLM
OT  - Adaptive immunity
OT  - Cytokines
OT  - Immunology
OT  - T cells
OT  - Virology
COIS- Conflict of interest: LC is on the scientific advisory board for and holds stock 
      in Immune Design Corp. and is a coinventor listed on several patents involving 
      potential HSV vaccine development (US patents 6,375,952; 6,413,518; 6,855,317; 
      6,962,709; 7,078,041; 7,431,934; 7,666,434; 7,744,903; 8,852,602; and 9,675,688 
      and European Patent Office, international publication number WO2001/023414). JTS 
      received research funds from Genocea.
EDAT- 2020/03/04 06:00
MHDA- 2021/02/03 06:00
PMCR- 2020/09/01
CRDT- 2020/03/04 06:00
PHST- 2019/08/16 00:00 [received]
PHST- 2020/02/11 00:00 [accepted]
PHST- 2020/03/04 06:00 [pubmed]
PHST- 2021/02/03 06:00 [medline]
PHST- 2020/03/04 06:00 [entrez]
PHST- 2020/09/01 00:00 [pmc-release]
AID - 132583 [pii]
AID - 10.1172/JCI132583 [doi]
PST - ppublish
SO  - J Clin Invest. 2020 Jun 1;130(6):2903-2919. doi: 10.1172/JCI132583.