Distribution of CCR5+ CD4+ cells in inner and outer foreskin

Background: Male circumcision reduces heterosexual HIV acquisition by as much as 60% and is currently encouraged by the World Health Organization as a prevention measure. The mechanism by which circumcision protects against infection is still poorly understood and requires further study. We hypothesize that the distribution of target cells in tissue is skewed towards vulnerability in uncircumcised men. Material & Methods: Inner and outer foreskin biopsies from 24 young males (18-24) were cryo-sectioned and stained for HIV-1 receptors CD4 and CCR5. Deconvolution fluorescence micrographs were manually analyzed for the presence of cells positive for one or both markers in the epithelium and sub-basal tissue, and for epithelial tissue area. Results : We find that the majority of CD4+ cells are also CCR5+. However, when we consider the two layers separately, we find that in the epithelium, the proportion of CD4+ cells that are CCR5+ is noticeably higher than in the sub-basal connective tissue. We observe this trend for both inner and outer foreskin. When consolidating data from all images for each donor we can calculate the inner-to-outer foreskin ratio of the preponderance of CCR5+ cells among CD4+ cells. We observe that the whole-tissue and sub-basal analyses yield a moderate bias towards ratios less than 1. This indicates that the preponderance of CCR5+ cells among CD4+ cells is somewhat lower in inner foreskin than in outer foreskin. However, considering the epithelium, the bias is slightly towards values greater than 1, indicating a higher preponderance of target cells in the inner foreskin. Conclusions: Our data supports the hypothesis that, in the epithelial layers, CD4+ cells are more likely to express the necessary HIV co-receptor CCR5 in inner foreskin than in outer foreskin.