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 Citations (Scopus)

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 2011
Externally publishedYes

Fingerprint

Human Herpesvirus 2
T-Lymphocytes
Epithelium
Viruses
Interleukin-4
Interleukin-5
Ovalbumin
Vaccines
Cytokines
Antigens
Infection
Population

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

Nelson, M. H., Bird, M. D., Chu, C. F., Johnson, A. J., Friedrich, B. M., Allman, W. R., & Milligan, G. N. (2011). Rapid clearance of herpes simplex virus type 2 by CD8+ T cells requires high level expression of effector T cell functions. Journal of Reproductive Immunology, 89(1), 10-17. https://doi.org/10.1016/j.jri.2011.01.013

Rapid clearance of herpes simplex virus type 2 by CD8+ T cells requires high level expression of effector T cell functions. / Nelson, Michelle H.; Bird, Melanie D.; Chu, Chin Fun; Johnson, Alison J.; Friedrich, Brian M.; Allman, Windy R.; Milligan, Gregg N.

In: Journal of Reproductive Immunology, Vol. 89, No. 1, 04.2011, p. 10-17.

Research output: Contribution to journalArticle

Nelson, Michelle H. ; Bird, Melanie D. ; Chu, Chin Fun ; Johnson, Alison J. ; Friedrich, Brian M. ; Allman, Windy R. ; Milligan, Gregg N. / Rapid clearance of herpes simplex virus type 2 by CD8+ T cells requires high level expression of effector T cell functions. In: Journal of Reproductive Immunology. 2011 ; Vol. 89, No. 1. pp. 10-17.
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