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.