title: Rapid clearance of herpes simplex virus type 2 by CD8+ T cells requires high level expression of effector T cell functions.
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.
authors: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors: Michelle H
authors: MH
authors: Nelson
authors: Melanie D
authors: MD
authors: Bird
authors: Chin-Fun
authors: CF
authors: Chu
authors: Alison J
authors: AJ
authors: Johnson
authors: Brian M
authors: BM
authors: Friedrich
authors: Windy R
authors: WR
authors: Allman
authors: Gregg N
authors: GN
authors: Milligan
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D049109:Cell Proliferation; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D004848:Epithelium / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D005260:Female; D005836:Genitalia, Female / Q000473:pathology; D006558:Herpes Genitalis / Q000276:immunology*; D018258:Herpesvirus 2, Human / Q000276:immunology* / Q000472:pathogenicity; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015847:Interleukin-4 / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D017471:Receptors, Interferon / Q000235:genetics; D058408:Th1-Th2 Balance; D019562:Viral Load / Q000235:genetics; D000096743:Interferon gamma Receptor
chemical_list: D007371:Interferon-gamma; D015847:Interleukin-4; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor