Functional attributes of mucosal immunity in cervical intraepithelial neoplasia and effects of HIV infection

Akiko Kobayashi, Ruth M. Greenblatt, Kathryn Anastos, Howard Minkoff, Leslie S. Massad, Mary Young, Alexandra M. Levine, Teresa M. Darragh, Vivian Weinberg, Karen K. Smith-McCune

Research output: Contribution to journalArticlepeer-review

94 Scopus citations

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-α 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-β+ CD25+ cells in the infiltrates associated with CIN lesions, and of immature CD1a+ dendritic cells expressing IL-10 and transforming growth factor-β, 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-γ 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 HTV-seropositive women.

Original languageEnglish (US)
Pages (from-to)6766-6774
Number of pages9
JournalCancer research
Volume64
Issue number18
DOIs
StatePublished - Sep 15 2004
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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