Rapid clearance of herpes simplex virus type 2 by CD8+ T cells requires high level expression of effector T cell functions

Michelle H. Nelson, Melanie D. Bird, Chin Fun Chu, Alison J. Johnson, Brian M. Friedrich, Windy R. Allman, Gregg N. Milligan

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

CD8+ T cells are important for resolution of HSV-2 lesions from the female genital epithelium. It is uncertain whether optimal clearance of viruses such as HSV-2 that cause a limited, non-systemic infection solely requires expression of effector functions by infiltrating CD8+ T lymphocytes, or if the clearance rate is reflective of the expression level of critical effector functions. To address this, CD8+ T cells from normal OT-I mice or OT-I mice deficient in IFNγ (IFNγ-/-) or the IFNγ receptor (IFNγR-/-) were activated in vitro in the presence of IFNγ or IL-4 to generate a series of effector populations (Tc1 and Tc2-like respectively) that secreted different levels of IFNγ and expressed different levels of HSV-specific cytolytic function. Compared with Tc1 cells, Tc2-like cells produced the type 2 cytokines IL-4 and IL-5, exhibited decreased IFNγ secretion, diminished proliferation in vitro, and decreased antigen-specific cytolysis in vivo. Clearance of an ovalbumin-expressing HSV-2 strain (HSV-2 tk- OVA) by adoptively transferred Tc2-like cells was delayed relative to Tc1 cell recipients. Because donor Tc2-like cells proliferated in vivo and infiltrated the infected genital epithelium similar to Tc1 cells, the diminished virus clearance by Tc2-like effector cells correlated with reduced expression of critical effector functions. Together, these results suggest that high level expression of protective T cell functions by effector T cells is necessary for optimal clearance of HSV-2 from the genital epithelium. These results have important implications for vaccines designed to elicit CD8+ T cells against viruses such as HSV-2 that infect the genital tract.

Original languageEnglish (US)
Pages (from-to)10-17
Number of pages8
JournalJournal of Reproductive Immunology
Volume89
Issue number1
DOIs
StatePublished - Apr 1 2011

    Fingerprint

Keywords

  • CD8+ t lymphocyte
  • Cytotoxicity
  • Female genital tract
  • Interferon-γ
  • Tumor necrosis factor-α

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Reproductive Medicine
  • Obstetrics and Gynecology

Cite this