title: Analysis of T cell responses during active varicella-zoster virus reactivation in human ganglia.
abstract: Varicella-zoster virus (VZV) is responsible for both varicella (chickenpox) and herpes zoster (shingles). During varicella, the virus establishes latency within the sensory ganglia and can reactivate to cause herpes zoster, but the immune responses that occur in ganglia during herpes zoster have not previously been defined. We examined ganglia obtained from individuals who, at the time of death, had active herpes zoster. Ganglia innervating the site of the cutaneous herpes zoster rash showed evidence of necrosis, secondary to vasculitis, or localized hemorrhage. Despite this, there was limited evidence of VZV antigen expression, although a large inflammatory infiltrate was observed. Characterization of the infiltrating T cells showed a large number of infiltrating CD4(+) T cells and cytolytic CD8(+) T cells. Many of the infiltrating T cells were closely associated with neurons within the reactivated ganglia, yet there was little evidence of T cell-induced neuronal apoptosis. Notably, an upregulation in the expression of major histocompatibility complex class I (MHC-I) and MHC-II molecules was observed on satellite glial cells, implying these cells play an active role in directing the immune response during herpes zoster. This is the first detailed characterization of the interaction between T cells and neuronal cells within ganglia obtained from patients suffering herpes zoster at the time of death and provides evidence that CD4(+) and cytolytic CD8(+) T cell responses play an important role in controlling VZV replication in ganglia during active herpes zoster.
  
  
  OBJECTIVE
  VZV is responsible for both varicella (chickenpox) and herpes zoster (shingles). During varicella, the virus establishes a life-long dormant infection within the sensory ganglia and can reawaken to cause herpes zoster, but the immune responses that occur in ganglia during herpes zoster have not previously been defined. We examined ganglia obtained from individuals who, at the time of death, had active herpes zoster. We found that specific T cell subsets are likely to play an important role in controlling VZV replication in ganglia during active herpes zoster.
authors.affiliation: Discipline of Infectious Diseases and Immunology, The University of Sydney, New South Wales, Australia.
authors.forename: Megan
authors.initials: M
authors.lastname: Steain
authors.forename: Jeremy P
authors.initials: JP
authors.lastname: Sutherland
authors.forename: Michael
authors.initials: M
authors.lastname: Rodriguez
authors.forename: Anthony L
authors.initials: AL
authors.lastname: Cunningham
authors.forename: Barry
authors.initials: B
authors.lastname: Slobedman
authors.forename: Allison
authors.initials: A
authors.lastname: Abendroth
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000956:Antigens, Viral / Q000276:immunology / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002648:Child; D005260:Female; D017950:Ganglia, Sensory / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D006562:Herpes Zoster / Q000276:immunology*; D014645:Herpesvirus 3, Human / Q000502:physiology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000276:immunology / Q000473:pathology / Q000821:virology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism; D014775:Virus Activation / Q000276:immunology*; D055815:Young Adult
chemical_list: D000956:Antigens, Viral; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D053148:Caspase 3