HIV Infection in Uncircumcised Men is Associated with Altered CD8 T-cell Function but Normal CD4 T-cell Numbers in the Foreskin

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.

Keywords

Circumcision, Cytokines, HIV, Sexually transmitted infections, T cells

Citation

Prodger, J. L., Hirbod, T., Gray, R., Kigozi, G., Nalugoda, F., Galiwango, R., ... & Ambrose, B. (2014). 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, 209(8), 1185-1194. DOI: 10.1093/infdis/jit644

URI

https://nru.uncst.go.ug/xmlui/handle/123456789/781

Collections

Medical and Health Sciences

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