Foreskin T cell subsets differ substantially from blood with respect to HIV co-receptor expression, inflammatory profile and memory status

Abstract

The foreskin is the main site of heterosexual HIV acquisition in uncircumcised men, but functional data regarding T cells subsets present at this site are lacking. Foreskin tissue and blood were obtained from Ugandan men undergoing elective adult circumcision. Tissue was treated by mechanical and enzymatic digestion followed by T cell subset identification and assessment of cytokine production using flow cytometery. Foreskin CD4 ⁺ T cells were predominantly an effector memory phenotype, and compared to blood they displayed a higher frequency of CCR5 expression (42.0% vs. 9.9%) and IL-17 production. There was no difference in T regulatory cell frequency, but IFNγ and TNFα production were increased in foreskin CD8 ⁺ T cells. These novel techniques demonstrate that the foreskin represents a pro-inflammatory milieu that is enriched for HIV-susceptible T cell subsets. Further characterization of foreskin T cell subsets may help to define the correlates of HIV susceptibility in the foreskin.