title: Distribution and Activation of CD8+ T Cells in the Duodenal Mucosa before and after HIV Seroconversion.
abstract: CD8+T cells in the intestinal mucosa influence the HIV-associated pathogenesis, but little is known about the dynamics of mucosal CD8+T cell counts and activation of these cells during the course of infection. In this study, mucosal CD8+T cells in the duodenum were studied at different stages of HIV infection, starting from the seronegative phase. In seronegative acute HIV infection, CD8+T cell counts increased in the epithelium, but not in the lamina propria. Infiltration of the lamina propria by peripherally expanded CD8+T cells was observed after seroconversion. Highest increase in the expression of perforin, the rate-limiting molecule for cytotoxic CD8+T cell activity, was evident in the lamina propria of seronegative acutely HIV-infected patients. The number of perforin-expressing cells in the lamina propria of acutely HIV-infected patients was positively associated with biomarkers of enterocyte damage and microbial translocation. After seroconversion, perforin expression was downregulated in the lamina propria, but not in the epithelium. In conclusion, our findings demonstrate that intraepithelial and lamina propria CD8+T cells exhibit different dynamics of numerical alteration and cytotoxic activity in HIV-infected patients. Moreover, our results suggest that perforin-dependent cytotoxic mechanisms by CD8+T cells could impair the intestinal mucosal barrier already in the seronegative phase of acute HIV infection, thereby inducing microbial translocation as one of the earliest pathological events in HIV infection.
authors.affiliation: Department of Gastroenterology, Infectious Diseases, and Rheumatology, Charité-University Medicine Berlin, 12203 Berlin, Germany; kristina.allers@charite.de.
authors.forename: Kristina
authors.initials: K
authors.lastname: Allers
authors.affiliation: Department of Gastroenterology, Infectious Diseases, and Rheumatology, Charité-University Medicine Berlin, 12203 Berlin, Germany.|Department of Immunology, Max Planck Institute for Infection Biology, 10117 Berlin, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Puyskens
authors.affiliation: Department of Gastroenterology, Infectious Diseases, and Rheumatology, Charité-University Medicine Berlin, 12203 Berlin, Germany.
authors.forename: Hans-Jörg
authors.initials: HJ
authors.lastname: Epple
authors.affiliation: Division of Infectious Disease and Pulmonary Medicine, Department of Internal Medicine, Charité-University Medicine Berlin, 13353 Berlin, Germany; and.
authors.forename: Dirk
authors.initials: D
authors.lastname: Schürmann
authors.affiliation: Institute of Medical Virology, Charité-University Medicine Berlin, 10117 Berlin, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Hofmann
authors.affiliation: Department of Gastroenterology, Infectious Diseases, and Rheumatology, Charité-University Medicine Berlin, 12203 Berlin, Germany.
authors.forename: Verena
authors.identifier: 0000-0002-9558-7291
authors.initials: V
authors.lastname: Moos
authors.affiliation: Department of Gastroenterology, Infectious Diseases, and Rheumatology, Charité-University Medicine Berlin, 12203 Berlin, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schneider
mesh_terms: D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004386:Duodenum / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000276:immunology*; D006679:HIV Seropositivity / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D055815:Young Adult