Anna Gibbs1, Marcus Buggert2,3,4, Gabriella Edfeldt1, Petter Ranefall5, Andrea Introini1, Stanley Cheuk1, Elisa Martini1, Liv Eidsmo1, Terry B Ball6,7, Joshua Kimani8, Rupert Kaul9, Annika C Karlsson4, Carolina Wählby5, Kristina Broliden1, Annelie Tjernlund1. 1. Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden. 2. Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia. 3. Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia. 4. Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden. 5. Department of Information Technology, Centre for Image Analysis, Uppsala University, Science for Life Laboratory, Sweden. 6. Department of Medical Microbiology, University of Manitoba, Winnipeg, Canada. 7. National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg. 8. Department of Medical Microbiology, Kenyatta National Hospital, University of Nairobi, Kenya. 9. Department of Medicine and Immunology, University of Toronto, Canada.
Abstract
Background: Genital mucosa is the main portal of entry for various incoming pathogens, including human immunodeficiency virus (HIV), hence it is 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. In this study, 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: Although the ectocervical epithelium of healthy women was populated with bona fide CD8+ TRM cells (CD103+CD69+), women infected with HIV displayed a 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. In addition, women infected with HIV 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.
Background: Genital mucosa is the main portal of entry for various incoming pathogens, including human immunodeficiency virus (HIV), hence it is 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. In this study, we describe the composition of CD8+ TRM cells in the ectocervix of healthy and HIV-infectedwomen. 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: Although the ectocervical epithelium of healthy women was populated with bona fide CD8+ TRM cells (CD103+CD69+), women infected with HIV displayed a 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-infectedwomen. In addition, women infected with HIV 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.
Authors: Laura Pattacini; Amanda Woodward Davis; Julie Czartoski; Florian Mair; Scott Presnell; Sean M Hughes; Ollivier Hyrien; Gretchen M Lentz; Anna C Kirby; Michael F Fialkow; Florian Hladik; Martin Prlic; Jennifer M Lund Journal: Mucosal Immunol Date: 2019-07-16 Impact factor: 8.701