Distribution of Immune Cells in the Human Cervix and Implications for <scp>HIV</scp> Transmission

Abstract

PROBLEM: Knowledge of the mucosal immune cell composition of the human female genital tract is important for understanding susceptibility to HIV-1. METHOD OF STUDY: We developed an optimized procedure for multicolor flow cytometry analysis of immune cells from human cervix to characterize all major immune cell subsets in the endocervix and ectocervix. RESULTS: Half of tissue hematopoietic cells were CD14(+) , many of which were macrophages and about a third were CD11c(+) , most of which were CD103(-) CD11b(+) CX3CR1(+) DC-SIGN(+) dendritic cells (DCs). The other dominant population were T cells, with more CD8 than CD4 cells. T cells (both CD8 and CD4) and B cells were more abundant in the ectocervix than endocervix of pre-menopausal women; however, CD8(+) T cell and B cell numbers declined in the ectocervix after menopause, while CD4 T cell counts remained higher. B, NK and conventional myeloid and plasmocytoid DCs each were a few percent of tissue hematopoietic cells. Although the ectocervix had more HIV-susceptible CD4(+) T cells, polarized endocervical explants supported HIV replication significantly better. CONCLUSION: Due to their abundance in the genital tract, CX3CR1(+) DC-SIGN(+) DCs might be important in HIV transmission. Our data also suggest that the columnar epithelium of the upper genital tract might be a preferential site for HIV transmission.