T-cell-mediated mechanisms involved in resolution of genital herpes simplex virus type 2 (HSV-2) infection of mice

Gregg Milligan, Kristen L. Dudley-McClain, Christal G. Young, Chin Fun Chu

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Resolution of a HSV-2 infection of the female genital tract has been shown to be T-cell dependent. The T-cell populations and mechanisms involved in clearance of virus from the genital epithelium were examined in this study. T lymphocytes expressing either αβ or γδ T-cell receptors (TCR) have been detected in the vaginal epithelium of mice. The involvement of γδ T cells in HSV-2 clearance was tested by intravaginal (ivag) challenge of mice depleted of αβ T cells by administration of specific antibodies and of mice lacking γδ T cells due to specific deletion of the δ TCR gene. The results of these studies strongly suggest that γδ T cells are not required for or involved in clearance of HSV-2 from the genital epithelium. Mechanisms of virus clearance employed by αβ T cells were also examined. Although HSV-specific lytic activity could be demonstrated ex vivo in populations of vaginal exudate cells from HSV-infected mice, clearance of virus did not require either perforin- or Fas/Fas ligand (FasL)-dependent cytolytic pathways. In contrast, virus resolution was significantly impaired following neutralization of interferon-gamma (IFN-γ), but not tumor necrosis factor-alpha (TNF-α). Together, these results suggest that non-lytic mechanisms mediated by αβ T cells were responsible for resolution of a genital HSV-2 infection.

Original languageEnglish (US)
Pages (from-to)115-127
Number of pages13
JournalJournal of Reproductive Immunology
Volume61
Issue number2
DOIs
StatePublished - Apr 2004

Fingerprint

Herpes Genitalis
Human Herpesvirus 2
Virus Diseases
T-Lymphocytes
Viruses
Epithelium
T-Cell Receptor Genes
Perforin
Fas Ligand Protein
Exudates and Transudates
T-Cell Antigen Receptor
Population
Interferon-gamma
Tumor Necrosis Factor-alpha

Keywords

  • αβ T cell
  • γδ T cell
  • Cytotoxicity
  • Female genital tract
  • Herpes simplex virus
  • Interferon-gamma

ASJC Scopus subject areas

  • Immunology
  • Reproductive Medicine

Cite this

T-cell-mediated mechanisms involved in resolution of genital herpes simplex virus type 2 (HSV-2) infection of mice. / Milligan, Gregg; Dudley-McClain, Kristen L.; Young, Christal G.; Chu, Chin Fun.

In: Journal of Reproductive Immunology, Vol. 61, No. 2, 04.2004, p. 115-127.

Research output: Contribution to journalArticle

Milligan, Gregg ; Dudley-McClain, Kristen L. ; Young, Christal G. ; Chu, Chin Fun. / T-cell-mediated mechanisms involved in resolution of genital herpes simplex virus type 2 (HSV-2) infection of mice. In: Journal of Reproductive Immunology. 2004 ; Vol. 61, No. 2. pp. 115-127.
@article{fb49024b3e284627a369bdfe99e2c1fc,
title = "T-cell-mediated mechanisms involved in resolution of genital herpes simplex virus type 2 (HSV-2) infection of mice",
abstract = "Resolution of a HSV-2 infection of the female genital tract has been shown to be T-cell dependent. The T-cell populations and mechanisms involved in clearance of virus from the genital epithelium were examined in this study. T lymphocytes expressing either αβ or γδ T-cell receptors (TCR) have been detected in the vaginal epithelium of mice. The involvement of γδ T cells in HSV-2 clearance was tested by intravaginal (ivag) challenge of mice depleted of αβ T cells by administration of specific antibodies and of mice lacking γδ T cells due to specific deletion of the δ TCR gene. The results of these studies strongly suggest that γδ T cells are not required for or involved in clearance of HSV-2 from the genital epithelium. Mechanisms of virus clearance employed by αβ T cells were also examined. Although HSV-specific lytic activity could be demonstrated ex vivo in populations of vaginal exudate cells from HSV-infected mice, clearance of virus did not require either perforin- or Fas/Fas ligand (FasL)-dependent cytolytic pathways. In contrast, virus resolution was significantly impaired following neutralization of interferon-gamma (IFN-γ), but not tumor necrosis factor-alpha (TNF-α). Together, these results suggest that non-lytic mechanisms mediated by αβ T cells were responsible for resolution of a genital HSV-2 infection.",
keywords = "αβ T cell, γδ T cell, Cytotoxicity, Female genital tract, Herpes simplex virus, Interferon-gamma",
author = "Gregg Milligan and Dudley-McClain, {Kristen L.} and Young, {Christal G.} and Chu, {Chin Fun}",
year = "2004",
month = "4",
doi = "10.1016/j.jri.2003.12.002",
language = "English (US)",
volume = "61",
pages = "115--127",
journal = "Journal of Reproductive Immunology",
issn = "0165-0378",
publisher = "Elsevier Ireland Ltd",
number = "2",

}

TY - JOUR

T1 - T-cell-mediated mechanisms involved in resolution of genital herpes simplex virus type 2 (HSV-2) infection of mice

AU - Milligan, Gregg

AU - Dudley-McClain, Kristen L.

AU - Young, Christal G.

AU - Chu, Chin Fun

PY - 2004/4

Y1 - 2004/4

N2 - Resolution of a HSV-2 infection of the female genital tract has been shown to be T-cell dependent. The T-cell populations and mechanisms involved in clearance of virus from the genital epithelium were examined in this study. T lymphocytes expressing either αβ or γδ T-cell receptors (TCR) have been detected in the vaginal epithelium of mice. The involvement of γδ T cells in HSV-2 clearance was tested by intravaginal (ivag) challenge of mice depleted of αβ T cells by administration of specific antibodies and of mice lacking γδ T cells due to specific deletion of the δ TCR gene. The results of these studies strongly suggest that γδ T cells are not required for or involved in clearance of HSV-2 from the genital epithelium. Mechanisms of virus clearance employed by αβ T cells were also examined. Although HSV-specific lytic activity could be demonstrated ex vivo in populations of vaginal exudate cells from HSV-infected mice, clearance of virus did not require either perforin- or Fas/Fas ligand (FasL)-dependent cytolytic pathways. In contrast, virus resolution was significantly impaired following neutralization of interferon-gamma (IFN-γ), but not tumor necrosis factor-alpha (TNF-α). Together, these results suggest that non-lytic mechanisms mediated by αβ T cells were responsible for resolution of a genital HSV-2 infection.

AB - Resolution of a HSV-2 infection of the female genital tract has been shown to be T-cell dependent. The T-cell populations and mechanisms involved in clearance of virus from the genital epithelium were examined in this study. T lymphocytes expressing either αβ or γδ T-cell receptors (TCR) have been detected in the vaginal epithelium of mice. The involvement of γδ T cells in HSV-2 clearance was tested by intravaginal (ivag) challenge of mice depleted of αβ T cells by administration of specific antibodies and of mice lacking γδ T cells due to specific deletion of the δ TCR gene. The results of these studies strongly suggest that γδ T cells are not required for or involved in clearance of HSV-2 from the genital epithelium. Mechanisms of virus clearance employed by αβ T cells were also examined. Although HSV-specific lytic activity could be demonstrated ex vivo in populations of vaginal exudate cells from HSV-infected mice, clearance of virus did not require either perforin- or Fas/Fas ligand (FasL)-dependent cytolytic pathways. In contrast, virus resolution was significantly impaired following neutralization of interferon-gamma (IFN-γ), but not tumor necrosis factor-alpha (TNF-α). Together, these results suggest that non-lytic mechanisms mediated by αβ T cells were responsible for resolution of a genital HSV-2 infection.

KW - αβ T cell

KW - γδ T cell

KW - Cytotoxicity

KW - Female genital tract

KW - Herpes simplex virus

KW - Interferon-gamma

UR - http://www.scopus.com/inward/record.url?scp=1842611841&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=1842611841&partnerID=8YFLogxK

U2 - 10.1016/j.jri.2003.12.002

DO - 10.1016/j.jri.2003.12.002

M3 - Article

C2 - 15063634

AN - SCOPUS:1842611841

VL - 61

SP - 115

EP - 127

JO - Journal of Reproductive Immunology

JF - Journal of Reproductive Immunology

SN - 0165-0378

IS - 2

ER -