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 journalArticle

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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

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Mucosal Immunity
Cervical Intraepithelial Neoplasia
HIV Infections
Natural Killer Cells
HIV
T-Lymphocytes
Macrophages
Transforming Growth Factors
Interferons
Neutrophils
Cell Count
Cytokines
HIV-2
Interleukin-2 Receptors
Innate Immunity
Mast Cells
Cervix Uteri
Interleukin-10
Dendritic Cells

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Kobayashi, A., Greenblatt, R. M., Anastos, K., Minkoff, H., Massad, L. S., Young, M., ... Smith-McCune, K. K. (2004). Functional attributes of mucosal immunity in cervical intraepithelial neoplasia and effects of HIV infection. Cancer Research, 64(18), 6766-6774. https://doi.org/10.1158/0008-5472.CAN-04-1091

Functional attributes of mucosal immunity in cervical intraepithelial neoplasia and effects of HIV infection. / Kobayashi, Akiko; Greenblatt, Ruth M.; Anastos, Kathryn; Minkoff, Howard; Massad, Leslie S.; Young, Mary; Levine, Alexandra M.; Darragh, Teresa M.; Weinberg, Vivian; Smith-McCune, Karen K.

In: Cancer Research, Vol. 64, No. 18, 15.09.2004, p. 6766-6774.

Research output: Contribution to journalArticle

Kobayashi, A, Greenblatt, RM, Anastos, K, Minkoff, H, Massad, LS, Young, M, Levine, AM, Darragh, TM, Weinberg, V & Smith-McCune, KK 2004, 'Functional attributes of mucosal immunity in cervical intraepithelial neoplasia and effects of HIV infection', Cancer Research, vol. 64, no. 18, pp. 6766-6774. https://doi.org/10.1158/0008-5472.CAN-04-1091
Kobayashi, Akiko ; Greenblatt, Ruth M. ; Anastos, Kathryn ; Minkoff, Howard ; Massad, Leslie S. ; Young, Mary ; Levine, Alexandra M. ; Darragh, Teresa M. ; Weinberg, Vivian ; Smith-McCune, Karen K. / Functional attributes of mucosal immunity in cervical intraepithelial neoplasia and effects of HIV infection. In: Cancer Research. 2004 ; Vol. 64, No. 18. pp. 6766-6774.
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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.",
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