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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

TitleHIV Infection in Uncircumcised Men Is Associated With Altered CD8 T-cell Function But Normal CD4 T-cell Numbers in the Foreskin
Publication TypeJournal Article
Year of Publication2014
AuthorsProdger, JL, Hirbod, T, Gray, R, Kigozi, G, Nalugoda, F, Galiwango, R, Reynolds, SJ, Huibner, S, Wawer, MJ, Serwadda, D, Kaul, R
JournalThe Journal of Infectious Diseases
Volume209
Pagination1185-94
Date PublishedApr 15
ISBN Number0022-1899
Accession Number24277744
Keywordscircumcision, cytokines, HIV, Sexual and Reproductive Health, sexually transmitted infections, T cells
Abstract

BACKGROUND: 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/mm(2); P < .001); but foreskin CD4 T-cell density was unchanged (43.0 vs 33.7/mm(2); P = .67), despite substantial blood depletion (409.0 vs 877.8 cells/microL; 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 alpha (TNFalpha) 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 TNFalpha may enhance susceptibility to genital coinfections in HIV+ men.

PMCID

Pmc3969543