Annelie Tjernlund [1], Anna Gibbs[1], Marcus Buggert [2-4], Gabriella Edfeldt [1], Petter Ranefall [5], Andrea Introini [1], Stanley Cheuk [1], Elisa Martini [1], Liv Eidsmo [1], Terry B. Ball [6,7], Joshua Kimani [8], Rupert Kaul [9], Annika C. Karlsson [4], Carolina Wählby [5] Kristina Broliden [1].
Affiliates: [1] Department of Medicine Solna, Karolinska Institutet, Sweden. [2] Department of Microbiology, University of Pennsylvania, USA. [3] Institute for Immunology, University of Pennsylvania, USA. [4] Department of Medicine Huddinge, Karolinska Institutet, Sweden. [5] Department of Information Technology, Uppsala University, Science for Life Laboratory, Sweden. [6] Department of Medical Microbiology, University of Manitoba, Canada. [7] National Microbiology Laboratory, Public Health Agency of Canada, Canada. [8] Department of Medical Microbiology, University of Nairobi, Kenya. [9] Department of Medicine and Immunology, University of Toronto, Toronto, Canada.

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.

Study samples were collected from the Swedish healthy 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.

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.

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.