Presence of HSV-1 immediate early genes and clonally expanded T-cells with a memory effector phenotype in human trigeminal ganglia.
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.
Derfuss
Tobias
T
Institute of Clinical Neuroimmunology, University Clinic, Munich, Germany. tsderfus@neuro.mpg.de
Segerer
Stephan
S
Herberger
Simone
S
Sinicina
Inga
I
Hüfner
Katharina
K
Ebelt
Kathleen
K
Knaus
Hans-Gunther
HG
Steiner
Israel
I
Meinl
Edgar
E
Dornmair
Klaus
K
Arbusow
Viktor
V
Strupp
Michael
M
Brandt
Thomas
T
Theil
Diethilde
D
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D018925:Chemokines / Q000276:immunology / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000235:genetics / Q000276:immunology; D002999:Clone Cells / Q000276:immunology / Q000821:virology; D005260:Female; D015967:Gene Expression Regulation, Viral / Q000235:genetics; D017781:Genes, Immediate-Early / Q000235:genetics*; D005814:Genes, Viral / Q000235:genetics; D006561:Herpes Simplex / Q000235:genetics* / Q000503:physiopathology / Q000821:virology*; D018259:Herpesvirus 1, Human / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory / Q000235:genetics / Q000276:immunology; D051664:Kv1.3 Potassium Channel / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009475:Neurons, Afferent / Q000276:immunology / Q000821:virology; D010641:Phenotype; D019707:Receptors, Chemokine / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology*; D012668:Trigeminal Ganglion / Q000166:cytology / Q000276:immunology / Q000821:virology*; D017735:Virus Latency / Q000235:genetics / Q000276:immunology