HIV-infected women have high numbers of CD103-CD8+ T cells residing close to the basal membrane of the ectocervical epithelium.

Abstract

BACKGROUND: Genital mucosa is the main portal of entry for various incoming pathogens, including HIV, hence an important site for host immune defenses. Tissue-resident memory T (TRM) cells defend tissue barriers against infections and are characterized by expression of CD103 and CD69. Here we describe the composition of CD8+ TRM cells in the ectocervix of healthy and HIV-infected women.

METHODS: Study samples were collected from healthy Swedish and Kenyan HIV-infected and uninfected women. Customized computerized image-based in situ analysis was developed to assess the ectocervical biopsies. Genital mucosa and blood samples were assessed by flow cytometry.

RESULTS: While ectocervical epithelium of healthy women was populated with bona fide CD8+ TRM cells (CD103+CD69+), HIV-infected women displayed high frequency of CD103-CD8+ cells residing close to their epithelial basal membrane. Accumulation of CD103-CD8+ cells was associated with chemokine expression in the ectocervix and HIV viral load. CD103+CD8+ and CD103-CD8+ T cells expressed cytotoxic effector molecules in the ectocervical epithelium of healthy and HIV-infected women. Additionally, HIV-infected women had decreased frequencies of circulating CD103+CD8+ T cells.

CONCLUSIONS: Our data provide insight into the distribution of CD8+ TRM cells in human genital mucosa, a critically important location for immune defense against pathogens, including HIV.