title: Immune Dysregulation in Patients Persistently Infected with Human Papillomaviruses 6 and 11.
abstract: Human Papillomaviruses (HPVs) 6 and 11 are part of a large family of small DNA viruses, some of which are commensal. Although much of the population can contain or clear infection with these viruses, there is a subset of individuals who develop persistent infection that can cause significant morbidity and on occasion mortality. Depending on the site of infection, patients chronically infected with these viruses develop either recurrent, and on occasion, severe genital warts or recurrent respiratory papillomas that can obstruct the upper airway. The HPV-induced diseases described are likely the result of a complex and localized immune suppressive milieu that is characteristic of patients with persistent HPV infection. We review data that documents impaired Langerhans cell responses and maturation, describes the polarized adaptive T-cell immune responses made to these viruses, and the expression of class select II MHC and KIR genes that associate with severe HPV6 and 11 induced disease. Finally, we review evidence that documents the polarization of functional TH2 and T-regulatory T-cells in tissues persistently infected with HPV6 and 11, and we review evidence that there is suppression of natural killer cell function. Together, these altered innate and adaptive immune responses contribute to the cellular and humoral microenvironment that supports HPV 6 and 11-induced disease.
authors.affiliation: Feinstein Institute for Medical Research, Manhasset, NY 11030, USA.
authors.forename: Alexandra V
authors.initials: AV
authors.lastname: Lucs
authors.affiliation: Feinstein Institute for Medical Research, Manhasset, NY 11030, USA ; Division of Allergy and Immunology, Department of Pediatrics, Hofstra North Shore-LIJ School of Medicine, Great Neck, NY 11549, USA.
authors.forename: James A
authors.initials: JA
authors.lastname: DeVoti
authors.affiliation: Feinstein Institute for Medical Research, Manhasset, NY 11030, USA ; Division of Allergy and Immunology, Department of Pediatrics, Hofstra North Shore-LIJ School of Medicine, Great Neck, NY 11549, USA.
authors.forename: Lynda
authors.initials: L
authors.lastname: Hatam
authors.affiliation: Feinstein Institute for Medical Research, Manhasset, NY 11030, USA ; Elmezzi Graduate School of Molecular Medicine, Manhasset, NY 11030, USA.
authors.forename: Ali
authors.initials: A
authors.lastname: Afzal
authors.affiliation: Feinstein Institute for Medical Research, Manhasset, NY 11030, USA ; Department of Otolaryngology, Hofstra North Shore-LIJ School of Medicine, New Hyde Park, NY 11549, USA.
authors.forename: Allan L
authors.initials: AL
authors.lastname: Abramson
authors.affiliation: Feinstein Institute for Medical Research, Manhasset, NY 11030, USA ; Elmezzi Graduate School of Molecular Medicine, Manhasset, NY 11030, USA ; Department of Otolaryngology, Hofstra North Shore-LIJ School of Medicine, New Hyde Park, NY 11549, USA ; Department of Molecular Medicine, Hofstra North Shore-LIJ School of Medicine, Manhasset, NY 11549, USA.
authors.forename: Bettie M
authors.initials: BM
authors.lastname: Steinberg
authors.affiliation: Feinstein Institute for Medical Research, Manhasset, NY 11030, USA ; Division of Allergy and Immunology, Department of Pediatrics, Hofstra North Shore-LIJ School of Medicine, Great Neck, NY 11549, USA ; Elmezzi Graduate School of Molecular Medicine, Manhasset, NY 11030, USA.
authors.forename: Vincent R
authors.initials: VR
authors.lastname: Bonagura
keywords: HPV; Langerhans cells; T cells; anogenital warts; innate immunity; natural killer cells; recurrent respiratory papillomatosis