PMID- 21429183
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20110714
LR  - 20220318
IS  - 2042-4280 (Electronic)
IS  - 2042-4280 (Linking)
VI  - 2
IP  - 1
DP  - 2011 Mar 15
TI  - Circulating herpes simplex type 1 (HSV-1)-specific CD8+ T cells do not access 
      HSV-1 latently infected trigeminal ganglia.
PG  - 5
LID - 10.1186/2042-4280-2-5 [doi]
AB  - BACKGROUND: Therapeutic vaccines can be designed to enhance existing T cell 
      memory populations for increased protection against re-infection. In the case of 
      herpes simplex virus type 1, recurrent disease results from reactivation of 
      latent virus in sensory ganglia, which is controlled in part by a 
      ganglia-resident HSV-specific memory CD8+ T cell population. Thus, an important 
      goal of a therapeutic HSV-1 vaccine would be to enhance this population. METHODS: 
      HSV-1-infected mice were treated with TAK-779 to block CCR5- and CXCR3-mediated 
      CD8+ T cell migration during both acute and latent infections. Additionally, 
      HSV-1-specific CD8+ T cells were transferred into HSV-1 latently infected mice to 
      mimic the effect of a therapeutic vaccine, and their migration into trigeminal 
      ganglia (TG) was traced during steady-state latency, or during recovery of the 
      TG-resident memory CD8+ T cell population following stress-, and 
      corticosterone-induced depletion and HSV-1 reactivation from latency. Bromodeoxy 
      uridine (BrdU) incorporation measured cell proliferation in vivo. RESULTS: 
      TAK-779 treatment during acute HSV-1 infection reduced the number of infiltrating 
      CD8+ T cells but did not alter the number of viral genome copies. TAK-779 
      treatment during HSV latency did not affect the size of the TG-resident memory 
      CD8+ T cell population. Transferred HSV-specific CD8+ T cells failed to access 
      latently infected TG during steady-state latency, or during recovery of the TG 
      resident HSV-specific CD8+ T cell population following exposure of latently 
      infected mice to stress and corticosterone. Recovery of the HSV-specific CD8+ T 
      cell population after stress and corticosterone treatment occurred with 
      homeostatic levels of cell division and did not require CD4+ T cell help. 
      CONCLUSIONS: Our findings are consistent with the notion that the CD8+ T cells in 
      latently infected TG are a tissue-resident memory (Trm) population that is 
      maintained without replenishment from the periphery, and that when this 
      population is disrupted, it recovers without proliferation or detectable 
      recruitment of HSV-specific CD8+ T cells from the blood. The compartmentalization 
      of the HSV-specific CD8+ memory T cell population in latently infected TG will 
      complicate the design of therapeutic vaccines.
FAU - Himmelein, Susanne
AU  - Himmelein S
AD  - Department of Neurology, Klinikum Grosshadern, Ludwig-Maximilians University, 
      Munich, Germany.
FAU - St Leger, Anthony J
AU  - St Leger AJ
AD  - Department of Ophthalmology, University of Pittsburgh School of Medicine, 
      Pittsburgh, PA 15213 USA.
AD  - Department of Immunology, University of Pittsburgh School of Medicine, 
      Pittsburgh, PA 15213 USA.
FAU - Knickelbein, Jared E
AU  - Knickelbein JE
AD  - Department of Ophthalmology, University of Pittsburgh School of Medicine, 
      Pittsburgh, PA 15213 USA.
FAU - Rowe, Alexander
AU  - Rowe A
AD  - Department of Ophthalmology, University of Pittsburgh School of Medicine, 
      Pittsburgh, PA 15213 USA.
FAU - Freeman, Michael L
AU  - Freeman ML
AD  - Trudeau Institute, Saranac Lake, NY 12983 USA.
FAU - Hendricks, Robert L
AU  - Hendricks RL
AD  - Department of Ophthalmology, University of Pittsburgh School of Medicine, 
      Pittsburgh, PA 15213 USA.
AD  - Department of Immunology, University of Pittsburgh School of Medicine, 
      Pittsburgh, PA 15213 USA.
AD  - Department of Molecular Genetics & Biochemistry, University of Pittsburgh, 
      Pittsburgh, PA 15213 USA.
LA  - eng
PT  - Journal Article
DEP - 20110315
PL  - England
TA  - Herpesviridae
JT  - Herpesviridae
JID - 101551529
PMC - PMC3070622
EDAT- 2011/03/25 06:00
MHDA- 2011/03/25 06:01
PMCR- 2011/03/15
CRDT- 2011/03/25 06:00
PHST- 2010/11/23 00:00 [received]
PHST- 2011/03/15 00:00 [accepted]
PHST- 2011/03/25 06:00 [entrez]
PHST- 2011/03/25 06:00 [pubmed]
PHST- 2011/03/25 06:01 [medline]
PHST- 2011/03/15 00:00 [pmc-release]
AID - 2042-4280-2-5 [pii]
AID - 10.1186/2042-4280-2-5 [doi]
PST - epublish
SO  - Herpesviridae. 2011 Mar 15;2(1):5. doi: 10.1186/2042-4280-2-5.