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Background:  Women now account for 50% of adult HIV-1 infection worldwide and 58% of adult infections in Sub-Saharan Africa. Blocking the CCR5 coreceptor for HIV-1 on genital mucosal cells may be an effective method to prevent heterosexual HIV infection. CCR5 inhibitors are currently in phase I/II clinical studies as antiretroviral agents and could be studied as topical microbicides to prevent HIV infection in healthy women. However HIV co-receptor expression in female genital mucosal cells is not well described.

Methods:  We collected endocervical cell specimens using a cytobrush at midcycle from 14 healthy women. All participants tested negative for pregnancy, HIV, syphilis, gonorrhea, chlamydia, HSV, HPV, trichomonas, and vaginal inflammation. Venous blood was collected for isolation of PBMC. The cytobrush specimen was vortexed in PBS, centrifuged, and resulting cell concentration adjusted to 0.5 to 1.0 x 10⁶ cells/mL. Cervical cells and PBMC were labeled with anti-CCR5, anti-CXCR4, anti-CD8, anti-CD4, anti-CD45RA, and anti-CD62L monoclonal antibodies and analyzed by flow cytometry to determine cellular phenotype, activation state and chemokine co-receptor expression. 

Results:  Matched PBMC and cervical cell specimens from 10 subjects were included. Four samples were excluded due to insufficient cervical lymphocyte counts (< 2500 cells/mL). Cervical CD4⁺ lymphocytes had significantly higher levels of CCR5 and CXCR4 expression than peripheral CD4⁺ lymphocytes. Cervical CD8⁺ lymphocytes also had significantly higher levels of CCR5 but not CXCR4 expression than peripheral CD8⁺ lymphocytes. CXCR4 was expressed on a higher proposrtion of peripheral CD4⁺ and CD8⁺ lymphocytes than CCR5, while the expression of CCR5 and CXCR4 did not differ significantly on cervical CD4⁺ and CD8⁺ lymphocytes

Conclusions:  Our data suggest that T lymphocyte HIV co-receptor expression differs in the peripheral and genital compartments of healthy women. Expression of both CCR5 and CXCR4 was high in the cervix, with at least 40% of CD4⁺ and CD8⁺ lymphocytes expressing these coreceptors. CCR5 inhibitors as topical or systemic microbicides may be a powerful method to prevent sexual HIV transmission in women. However the functional role of CCR5 and CXCR4 coreceptors in the genital tract should be examined, and studies of CCR5 inhibitors in healthy women should include evaluation of immunologic effects of CCR5 inhibition in the genital tract.

Keywords: CCR5; microbicides; genital immunology