PMID- 17784877 OWN - NLM STAT- MEDLINE DCOM- 20071221 LR - 20210904 IS - 1015-6305 (Print) IS - 1750-3639 (Electronic) IS - 1015-6305 (Linking) VI - 17 IP - 4 DP - 2007 Oct TI - Presence of HSV-1 immediate early genes and clonally expanded T-cells with a memory effector phenotype in human trigeminal ganglia. PG - 389-98 AB - The latent persistence of herpes simplex virus type 1 (HSV-1) in human trigeminal ganglia (TG) is accompanied by a chronic CD8 T-cell infiltrate. The focus of the current work was to look for HSV-1 transcription activity as a potential trigger of the immune response and to characterize the immune cell infiltrates by this feature. We combined in situ hybridization, laser cutting microscopy, and single cell RT-PCR to demonstrate the expression of the HSV-1 immediate early (IE) genes ICP0 and ICP4 in human trigeminal neurons. Using CDR3 spectratyping, we showed that the infiltrating T-cells are clonally expanded, indicating an antigen-driven immune response. Moreover, the persisting CD8+ T-cells had features of the memory effector phenotype. The voltage-gated potassium channel Kv1.3, a marker of chronic activated memory effector cells, and the chemokines CCL5 and CXCL10 were expressed by a subpopulation of infiltrating cells. The corresponding chemokine receptors CCR5 and CXCR3 were co-expressed on virtually all CD8 T-cells. In addition, T-cells expressed granzymes and perforin. In contrast to animal models of HSV-1 latency, hardly any FoxP3-positive regulatory T-cells were detected in human TG. Thus, HSV-1 IE genes are expressed in human TG and the infiltrating T-cells bear several characteristics that suggest viral antigenic stimulation. FAU - Derfuss, Tobias AU - Derfuss T AD - Institute of Clinical Neuroimmunology, University Clinic, Munich, Germany. tsderfus@neuro.mpg.de FAU - Segerer, Stephan AU - Segerer S FAU - Herberger, Simone AU - Herberger S FAU - Sinicina, Inga AU - Sinicina I FAU - Hufner, Katharina AU - Hufner K FAU - Ebelt, Kathleen AU - Ebelt K FAU - Knaus, Hans-Gunther AU - Knaus HG FAU - Steiner, Israel AU - Steiner I FAU - Meinl, Edgar AU - Meinl E FAU - Dornmair, Klaus AU - Dornmair K FAU - Arbusow, Viktor AU - Arbusow V FAU - Strupp, Michael AU - Strupp M FAU - Brandt, Thomas AU - Brandt T FAU - Theil, Diethilde AU - Theil D LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20070904 PL - Switzerland TA - Brain Pathol JT - Brain pathology (Zurich, Switzerland) JID - 9216781 RN - 0 (Chemokines) RN - 0 (Kv1.3 Potassium Channel) RN - 0 (Receptors, Chemokine) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - CD8-Positive T-Lymphocytes/immunology/virology MH - Chemokines/immunology/metabolism MH - Chemotaxis, Leukocyte/genetics/immunology MH - Clone Cells/immunology/virology MH - Female MH - Gene Expression Regulation, Viral/genetics MH - Genes, Immediate-Early/*genetics MH - Genes, Viral/genetics MH - Herpes Simplex/*genetics/physiopathology/*virology MH - Herpesvirus 1, Human/*genetics/immunology MH - Humans MH - Immunologic Memory/genetics/immunology MH - Kv1.3 Potassium Channel/metabolism MH - Male MH - Middle Aged MH - Neurons, Afferent/immunology/virology MH - Phenotype MH - Receptors, Chemokine/immunology/metabolism MH - T-Lymphocytes/immunology/*virology MH - Trigeminal Ganglion/cytology/immunology/*virology MH - Virus Latency/genetics/immunology PMC - PMC8095593 EDAT- 2007/09/06 09:00 MHDA- 2007/12/22 09:00 PMCR- 2007/09/04 CRDT- 2007/09/06 09:00 PHST- 2007/09/06 09:00 [pubmed] PHST- 2007/12/22 09:00 [medline] PHST- 2007/09/06 09:00 [entrez] PHST- 2007/09/04 00:00 [pmc-release] AID - BPA088 [pii] AID - 10.1111/j.1750-3639.2007.00088.x [doi] PST - ppublish SO - Brain Pathol. 2007 Oct;17(4):389-98. doi: 10.1111/j.1750-3639.2007.00088.x. Epub 2007 Sep 4.