Distribution of immune cells in the human cervix and implications for HIV transmission.

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.