title: Selective retention of herpes simplex virus-specific T cells in latently infected human trigeminal ganglia.
abstract: Primary infection with herpes simplex virus 1 (HSV-1) and varicella zoster virus (VZV) results in lifelong latent infections of neurons in sensory ganglia such as the trigeminal ganglia (TG). It has been postulated that T cells retained in TG inhibit reactivation of latent virus. The acquisition of TG specimens of individuals within hours after death offered the unique opportunity to characterize the phenotype and specificity of TG-resident T cells in humans. High numbers of activated CD8(+) T cells expressing a late effector memory phenotype were found to reside in latently infected TG. The T cell infiltrate was oligoclonal, and T cells selectively clustered around HSV-1 but not VZV latently infected neurons. Neuronal damage was not observed despite granzyme B expression by the neuron-interacting CD8(+) T cells. The TG-resident T cells, mainly CD8(+) T cells, were directed against HSV-1 and not to VZV, despite neuronal expression of VZV proteins. The results implicate that herpesvirus latency in human TG is associated with a local, persistent T cell response, comprising activated late effector memory CD8(+) T cells that appear to control HSV-1 latency by noncytolytic pathways. In contrast, T cells do not seem to be directly involved in controlling VZV latency in human TG.
authors.affiliation: Department of Virology, Erasmus Medical Center, Dr. Molewaterplein 50, 3015 GE, Rotterdam, The Netherlands. g.verjans@erasmusmc.nl
authors.forename: Georges M G M
authors.initials: GM
authors.lastname: Verjans
authors.forename: Rogier Q
authors.initials: RQ
authors.lastname: Hintzen
authors.forename: Jessica M
authors.initials: JM
authors.lastname: van Dun
authors.forename: Angelique
authors.initials: A
authors.lastname: Poot
authors.forename: Johannes C
authors.initials: JC
authors.lastname: Milikan
authors.forename: Jon D
authors.initials: JD
authors.lastname: Laman
authors.forename: Anton W
authors.initials: AW
authors.lastname: Langerak
authors.forename: Paul R
authors.initials: PR
authors.lastname: Kinchington
authors.forename: Albert D M E
authors.initials: AD
authors.lastname: Osterhaus
mesh_terms: D000911:Antibodies, Monoclonal; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D053804:Granzymes / Q000378:metabolism; D006566:Herpesviridae Infections / Q000276:immunology / Q000821:virology*; D018259:Herpesvirus 1, Human; D014645:Herpesvirus 3, Human; D006801:Humans; D007124:Immunoenzyme Techniques; D012668:Trigeminal Ganglion / Q000166:cytology / Q000821:virology*; D017735:Virus Latency / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D053804:Granzymes