title: Suppression of the CD8 T cell response by human papillomavirus type 16 E7 occurs in Langerhans cell-depleted mice.
abstract: Human papillomavirus (HPV) is an epitheliotropic virus that is the primary causal agent for cervical cancer. Langerhans cells (LC) are skin antigen presenting cells that are reduced in number in HPV-infected skin. The aim of this study was to understand the immune-modulatory effects of HPV16 E7 on LC and on the CD8 T cell response to a skin-expressed antigen. To test this, HPV16 E7 was expressed in mouse skin keratinocytes with the model antigen ovalbumin (Ova). Similar to what is observed in HPV-infected human skin, LC numbers were significantly reduced in E7-expressing mouse skin. This shows that expression of the E7 protein alone is sufficient to mediate LC depletion. Expression of E7 with Ova in keratinocytes strongly suppressed the Ova-specific CD8+T cell response in the skin draining lymph node. When tested in LC-ablated mice, the CD8 T cell response to skin-expressed Ova in control mice was not affected, nor was the T cell response to Ova restored in E7-expressing skin. These data indicate a role for E7 in regulation of LC homeostasis in the skin and in suppression of antigen specific CD8 T cell expansion, but suggest that these two effects occur independent of each other.
authors.affiliation: Department of Microbiology and Immunology, Otago School of Medical Sciences, University of Otago, Dunedin, New Zealand.
authors.forename: K
authors.initials: K
authors.lastname: Jemon
authors.affiliation: Department of Microbiology and Immunology, Otago School of Medical Sciences, University of Otago, Dunedin, New Zealand.
authors.forename: C-M
authors.initials: CM
authors.lastname: Leong
authors.affiliation: Department of Pathology, Dunedin School of Medicine, University of Otago, P O Box 56, Dunedin, New Zealand.
authors.forename: K
authors.initials: K
authors.lastname: Ly
authors.affiliation: Department of Pathology, Dunedin School of Medicine, University of Otago, P O Box 56, Dunedin, New Zealand.
authors.forename: S L
authors.initials: SL
authors.lastname: Young
authors.affiliation: Department of Microbiology and Immunology, Otago School of Medical Sciences, University of Otago, Dunedin, New Zealand.
authors.forename: A D
authors.initials: AD
authors.lastname: McLellan
authors.affiliation: Department of Pathology, Dunedin School of Medicine, University of Otago, P O Box 56, Dunedin, New Zealand.
authors.forename: M H
authors.initials: MH
authors.lastname: Hibma
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology* / Q000821:virology; D049109:Cell Proliferation; D015536:Down-Regulation; D004423:Ear / Q000473:pathology; D000078404:Epidermal Cells; D054884:Host-Pathogen Interactions; D007801:Langerhans Cells / Q000473:pathology / Q000821:virology*; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000378:metabolism; D050725:Papillomavirus E7 Proteins / Q000235:genetics / Q000378:metabolism*; D014161:Transduction, Genetic
chemical_list: D050725:Papillomavirus E7 Proteins; C059731:oncogene protein E7, Human papillomavirus type 16; D010047:Ovalbumin