title: Functional attributes of mucosal immunity in cervical intraepithelial neoplasia and effects of HIV infection.
abstract: The role of mucosal immunity in human papillomavirus (HPV)-related cervical diseases is poorly understood. To characterize the local immune microenvironment in cervical intraepithelial neoplasia (CIN) 2/3 and determine the effects of HIV infection, we compared samples from three groups: normal cervix, CIN 2/3 from immunocompetent women (HIV- CIN 2/3), and CIN 2/3 from HIV seropositive women (HIV+ CIN 2/3). CIN 2/3 lesions contained increased numbers of immune cells from both the acquired and innate arms of the immune response in stroma [CD4+ and CD8+ T cells, macrophages, mast cells, B cells, neutrophils, and natural killer (NK) cells] and dysplastic epithelium (CD4+ T cells, macrophages, and NK cells). Immune cells in CIN 2/3 expressed activation markers, as measured by interleukin-2 receptor (IL-2R) and transcription factor T bet. Interferon-gamma production was significantly up-regulated in CIN lesions and was expressed by CD4+ and CD8+ T cells and NK cells, indicating the activation of immune cells. Abundant presence of transforming growth factor-beta+ CD25+ cells in the infiltrates associated with CIN lesions, and of immature CD1a+ dendritic cells expressing IL-10 and transforming growth factor-beta, indicate that CIN is associated with an influx of immune cells that produce a mixture of proinflammatory and regulatory cytokines. In HIV+ CIN, immune cell densities (CD4+ T cells, macrophages, neutrophils, and NK cells) and expression of interferon-gamma were significantly decreased compared with HIV- CIN. Regulatory cytokines were also down-regulated in this group. Therefore, both pro- and anti-inflammatory responses present in CIN 2/3 lesions are suppressed in HIV-seropositive women.
authors.affiliation: The Cancer Research Institute and Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California at San Francisco, San Francisco, California 94143-0128, USA.
authors.forename: Akiko
authors.initials: A
authors.lastname: Kobayashi
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Greenblatt
authors.forename: Kathryn
authors.initials: K
authors.lastname: Anastos
authors.forename: Howard
authors.initials: H
authors.lastname: Minkoff
authors.forename: Leslie S
authors.initials: LS
authors.lastname: Massad
authors.forename: Mary
authors.initials: M
authors.lastname: Young
authors.forename: Alexandra M
authors.initials: AM
authors.lastname: Levine
authors.forename: Teresa M
authors.initials: TM
authors.lastname: Darragh
authors.forename: Vivian
authors.initials: V
authors.lastname: Weinberg
authors.forename: Karen K
authors.initials: KK
authors.lastname: Smith-McCune
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000276:immunology*; D006801:Humans; D018928:Immunity, Mucosal / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008875:Middle Aged; D002583:Uterine Cervical Neoplasms / Q000276:immunology* / Q000821:virology*; D002578:Uterine Cervical Dysplasia / Q000276:immunology* / Q000821:virology*
chemical_list: D016753:Interleukin-10; D007371:Interferon-gamma