Browsing by Author "Hirbod, Taha"

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    HIV Infection in Uncircumcised Men is Associated with Altered CD8 T-cell Function but Normal CD4 T-cell Numbers in the Foreskin
    (The Journal of infectious diseases, 2014) Prodger, Jessica L.; Hirbod, Taha; Gray, Ronald; Kigozi, Godfrey; Nalugoda, Fred; Galiwango, Ronald; Reynolds, Steven J.; Huibner, Sanja; Wawer, Maria J.; Serwadda, David; Kaul, Rupert; Rakai, Genital Immunology Research Group
    Human immunodeficiency virus (HIV)–infected (HIV+) men are more susceptible to sexually transmitted infections, and may be superinfected by HIV. We hypothesized that HIV induces immune alterations in the foreskin that may impact the subsequent acquisition/clearance of genital coinfections. Methods. Foreskin tissue and blood were obtained from 70 HIV-uninfected and 20 HIV+ men undergoing circumcision. T cells were characterized by flow cytometry, immunohistochemistry, and polymerase chain reaction. Results. There was substantial influx of CD8 T-cells into the foreskins of HIV+ men (108.8 vs 23.1 cells/mm2; P < .001); but foreskin CD4 T-cell density was unchanged (43.0 vs 33.7/mm2; P = .67), despite substantial blood depletion (409.0 vs 877.8 cells/μL; P < .001). While frequencies of foreskin C-C chemokine receptor type 5+ (CCR5+) T cells, T regulatory cells, and T-helper 17 cells were unaltered in HIV+ men, CD8 T-cell production of tumor necrosis factor α (TNFα) was decreased. HIV-specific CD8 T cells were present in the foreskins of HIV+ men, although their frequency and function was reduced compared to the blood. Conclusions. Foreskin CD4 T-cell density and CCR5 expression were not reduced during HIV infection, perhaps explaining susceptibility to HIV superinfection. Foreskin CD8 T-cell density was increased, but decreased production of TNFα may enhance susceptibility to genital coinfections in HIV+ men.
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    No Difference in Keratin Thickness between Inner and Outer Foreskins from Elective Male Circumcisions in Rakai, Uganda
    (PLoS ONE, 2012) Dinh, Minh H.; Hirbod, Taha; Kigozi, Godfrey; Okocha, Eneniziaogochukwu A.; Cianci, Gianguido C.; Kong, Xiangrong; Prodger, Jessica L.; Broliden, Kristina; Kaul, Rupert; Serwadda, David; Wawer, Maria J.; Gray, Ronald H.; Hope, Thomas J.
    It has been hypothesized that increased HIV acquisition in uncircumcised men may relate to a more thinly keratinized inner foreskin. However, published data are contradictory and potentially confounded by medical indications for circumcision. We tested the hypothesis that the inner foreskin was more thinly keratinized than the outer foreskin using tissues from 19 healthy, HIV-uninfected men undergoing routine prophylactic circumcision in Rakai, Uganda. Sections from 3 foreskin anatomic sites (inner, outer, and frenar band) were snap-frozen separately. Two independent laboratories each separately stained, imaged, and measured keratin thicknesses in a blinded fashion. There was no significant difference in keratin thickness between the inner (mean = 14.6767.48 mm) and outer (mean = 13.3068.49 mm) foreskin, or between the inner foreskin and the frenar band (mean = 16.91612.42 mm). While the frenar band showed the greatest intra-individual heterogeneity in keratin thickness, there was substantial inter-individual variation seen in all regions. Measurements made by the two laboratories showed high correlation (r = 0.741, 95% CI, 0.533–0.864). We conclude that, despite inter- and intra-individual variability, keratin thickness was similar in the inner and outer foreskin of healthy Ugandan men, and that reduced keratin thickness is not likely to make the inner foreskin more susceptible to HIV acquisition.