Bailey RC, Patterson B, Siegel J, Landay A; International Conference on AIDS.

Int Conf AIDS. 2002 Jul 7-12; 14: abstract no. ThPeC7414.

University of Illinois at Chicago, Chicago, United States

BACKGROUND: Over 35 epidemiological studies have found a significant protective effect of male circumcision (MC) against HIV acquisition. We studied mechanisms of HIV infection in foreskin tissue compared to cervical tissue by quantifying HIV target cells, chemokine receptor expression, and target cell infectivity with HIV-1. METHODS: Foreskins from pediatric and adult subjects with and without histories of STI infection were evaluated. CD4 T-cells, macrophages, and Langerhans cells (LC) were quantified using immunohistochemistry and image analysis. Cells expressing HIV-1 co-receptors CCR5 and CXCR4 were quantified using 2-color immunofluorescence and image analysis. Foreskin biopsies were infected ex-vivo in organotypic culture with HIV-1. Infected cell phenotype was determined by simultaneous immunophenotyping/ultrasensitive in situ hybridization. The quantity of HIV-1 DNA copies in foreskin and cervical mucosal tissue was compared. RESULTS: Foreskin mucosa contained immune cells with higher mean proportions of CD4 T cells (22%), macrophages (2%) and LCs (12%) in adults than in children (5%, 0.3%, 6%, respectively) or than in adult cervical mucosa (6%, 1%, 2%). The highest prortions of CD4 T cells and LCs occurred in subjects with history of infection. Foreskin mucosal cells expressed predominantly the CCR5 HIV-1 receptor. The keratinized outer surface of adult foreskin showed no uptake of HIV; whereas mucosa from the inner surface had several-fold greater susceptibility to infection with HIVbal than did cervical mucosa. CONCLUSIONS: Relative to cervical mucosa and external non-mucosal foreskin, foreskin mucosa have high proportions of HIV-1 target cells, especially T-cells and LCs, which express primarily CCR5, and are significantly more susceptible to ex-vivo HIV-1 infection. Circumcision likely reduces risk of HIV-1 acquisition in men by decreasing HIV-1 target cells and their receptors.

Publication Types:

• Meeting Abstracts

Keywords:

• AIDS Vaccines
• Acquired Immunodeficiency Syndrome
• Adult
• Animals
• Antigens, CD4
• Child
• Circumcision, Male
• Disease Susceptibility
• Epidemiologic Studies
• Female
• Genitalia, Female
• HIV
• HIV Core Protein p24
• HIV Infections
• HIV Seronegativity
• HIV Seropositivity
• HIV-1
• Humans
• Langerhans Cells
• Male
• Mucous Membrane
• Penis
• Receptors, CCR5
• Receptors, CXCR4
• Receptors, HIV
• Skin
• T-Lymphocytes
• immunology
• surgery

Other ID:

• GWAIDS0016211

UI: 102253709

From Meeting Abstracts