Peripheral Blood CD4 T-Cell and Plasmacytoid Dendritic Cell (pDC) Reactivity to Herpes Simplex Virus 2 and pDC Number Do Not Correlate with the Clinical or Virologic Severity of Recurrent Genital Herpes

Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington, USA.
Journal of Virology (Impact Factor: 4.44). 07/2012; 86(18):9952-63. DOI: 10.1128/JVI.00829-12
Source: PubMed

ABSTRACT Leukocytes participate in the immune control of herpes simplex virus (HSV). Data from HIV coinfections, germ line mutations, and case reports suggest involvement of CD4 T cells and plasmacytoid dendritic cells (pDC). We investigated the relationships between these cells and recurrent genital herpes disease severity in the general population. Circulating CD4 T-cell responses to HSV-2 were measured in specimens from 67 immunocompetent individuals with measured genital lesion and HSV shedding rates. Similarly, pDC number and functional responses to HSV-2 were analyzed in 40 persons. CD4 responses and pDC concentrations and responses ranged as much as 100-fold between persons while displaying moderate within-person consistency over time. No correlations were observed between these immune response parameters and genital HSV-2 severity. Cytomegalovirus (CMV) coinfection was not correlated with differences in HSV-2-specific CD4 T-cell responses. The CD4 T-cell response to HSV-2 was much more polyfunctional than was the response to CMV. These data suggest that other immune cell subsets with alternate phenotypes or anatomical locations may be responsible for genital herpes control in chronically infected individuals.

Download full-text


Available from: David M Koelle, Sep 27, 2015
36 Reads
  • Source
    • "T cell responses against HSV in humans are polyfunctional [119] and directed against a wide array of viral epitopes [120]. Infiltration of HSV-specific T cells into infected tissue initially involves CD4+ T cells, which in mice are required for subsequent CD8+ T cell entry into the mucosa [121]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Herpes simplex viruses types 1 and 2 (HSV-1 and HSV-2) infect a large proportion of the world's population. Infection is life-long and can cause periodic mucocutaneous symptoms, but it only rarely causes life-threatening disease among immunocompetent children and adults. However, when HSV infection occurs during the neonatal period, viral replication is poorly controlled and a large proportion of infants die or develop disability even with optimal antiviral therapy. Increasingly, specific differences are being elucidated between the immune system of newborns and those of older children and adults, which predispose to severe infections and reflect the transition from fetal to postnatal life. Studies in healthy individuals of different ages, individuals with primary or acquired immunodeficiencies, and animal models have contributed to our understanding of the mechanisms that control HSV infection and how these may be impaired during the neonatal period. This paper outlines our current understanding of innate and adaptive immunity to HSV infection, immunologic differences in early infancy that may account for the manifestations of neonatal HSV infection, and the potential of interventions to augment neonatal immune protection against HSV disease.
    Clinical and Developmental Immunology 03/2013; 2013(12):369172. DOI:10.1155/2013/369172 · 2.93 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Little is known concerning immunodominance within the CD4 T-cell response to viral infections and its persistence into long-term memory. We tested CD4 T-cell reactivity against each viral protein in persons immunized with vaccinia virus (VV), either recently or more than 40 years ago, as a model self-limited viral infection. Similar tests were done in persons with herpes simplex virus type 1 (HSV-1) infection as a model chronic infection. We used an indirect method capable of counting the number of CD4 T-cells in blood reactive with each individual viral protein. Each person had a clear CD4 T-cell dominance hierarchy. The top four open reading frames accounted for about 40% of CD4 virus-specific T-cells. Early and long-term memory CD4 T-cell responses to vaccinia were mathematically indistinguishable for antigen breadth and immunodominance. Despite the chronic intermittent presence of HSV-1 antigen, the CD4 T-cell dominance and diversity patterns for HSV-1 were identical to those observed for vaccinia. The immunodominant CD4 T-cell antigens included both long proteins abundantly present in virions, and shorter, non-structural proteins. Limited epitope-level and direct ex vivo data were also consistent with pronounced CD4 T-cell immunodominance. We conclude that human memory CD4 T-cell responses show a pattern of pronounced immunodominance for both chronic and self-limited viral infections, and that this pattern can persist over several decades in the absence of antigen.
    Journal of Virology 12/2012; 87(5). DOI:10.1128/JVI.03047-12 · 4.44 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Human alphaherpesviruses (αHHV)-herpes simplex virus type 1 (HSV-1), HSV-2, and varicella-zoster virus (VZV)-infect mucosal epithelial cells, establish a lifelong latent infection of sensory neurons, and reactivate intermittingly to cause recrudescent disease. Although chronic αHHV infections co-exist with brisk T-cell responses, T-cell immune suppression is associated with worsened recurrent infection. Induction of αHHV-specific T-cell immunity is complex and results in poly-specific CD4 and CD8 T-cell responses in peripheral blood. Specific T-cells are localized to ganglia during the chronic phase of HSV infection and to several infected areas during recurrences, and persist long after viral clearance. These recent advances hold promise in the design of new vaccine candidates.
    05/2013; 3(4). DOI:10.1016/j.coviro.2013.04.004
Show more