title: Enrichment of herpes simplex virus type 2 (HSV-2) reactive mucosal T cells in the human female genital tract.
abstract: Local mucosal cellular immunity is critical in providing protection from HSV-2. To characterize and quantify HSV-2-reactive mucosal T cells, lymphocytes were isolated from endocervical cytobrush and biopsy specimens from 17 HSV-2-infected women and examined ex vivo for the expression of markers associated with maturation and tissue residency and for functional T-cell responses to HSV-2. Compared with their circulating counterparts, cervix-derived CD4+ and CD8+ T cells were predominantly effector memory T cells (CCR7-/CD45RA-) and the majority expressed CD69, a marker of tissue residency. Co-expression of CD103, another marker of tissue residency, was highest on cervix-derived CD8+ T cells. Functional HSV-2 reactive CD4+ and CD8+ T-cell responses were detected in cervical samples and a median of 17% co-expressed CD103. HSV-2-reactive CD4+ T cells co-expressed IL-2 and were significantly enriched in the cervix compared with blood. This first direct ex vivo documentation of local enrichment of HSV-2-reactive T cells in the human female genital mucosa is consistent with the presence of antigen-specific tissue-resident memory T cells. Ex vivo analysis of these T cells may uncover tissue-specific mechanisms of local control of HSV-2 to assist the development of vaccine strategies that target protective T cells to sites of HSV-2 infection.
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.|Department of Laboratory Medicine, University of Washington, Seattle, Washington, USA.
authors.forename: C M
authors.initials: CM
authors.lastname: Posavad
authors.affiliation: Department of Laboratory Medicine, University of Washington, Seattle, Washington, USA.
authors.forename: L
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Medicine, University of Washington, Seattle, Washington, USA.
authors.forename: L
authors.initials: L
authors.lastname: Dong
authors.affiliation: Department of Laboratory Medicine, University of Washington, Seattle, Washington, USA.
authors.forename: L
authors.initials: L
authors.lastname: Jin
authors.affiliation: Department of Medicine, University of Washington, Seattle, Washington, USA.
authors.forename: C E
authors.initials: CE
authors.lastname: Stevens
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.|Department of Laboratory Medicine, University of Washington, Seattle, Washington, USA.|Department of Biostatistics, University of Washington, Seattle, Washington, USA.
authors.forename: A S
authors.initials: AS
authors.lastname: Magaret
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.|Department of Medicine, University of Washington, Seattle, Washington, USA.
authors.forename: C
authors.initials: C
authors.lastname: Johnston
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.|Department of Laboratory Medicine, University of Washington, Seattle, Washington, USA.|Department of Medicine, University of Washington, Seattle, Washington, USA.|Department of Epidemiology, University of Washington, Seattle, Washington, USA.
authors.forename: A
authors.initials: A
authors.lastname: Wald
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.|Department of Laboratory Medicine, University of Washington, Seattle, Washington, USA.
authors.forename: J
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.|Department of Laboratory Medicine, University of Washington, Seattle, Washington, USA.|Department of Medicine, University of Washington, Seattle, Washington, USA.
authors.forename: L
authors.initials: L
authors.lastname: Corey
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.|Department of Laboratory Medicine, University of Washington, Seattle, Washington, USA.|Department of Medicine, University of Washington, Seattle, Washington, USA.|Department of Global Health, University of Washington, Seattle, Washington, USA.|Benaroya Research Institute, Seattle, Washington, USA.
authors.forename: D M
authors.initials: DM
authors.lastname: Koelle
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D005260:Female; D005836:Genitalia, Female / Q000276:immunology* / Q000821:virology; D006558:Herpes Genitalis / Q000276:immunology*; D018258:Herpesvirus 2, Human / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D039001:Integrin alpha Chains / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D000075942:Intraepithelial Lymphocytes / Q000276:immunology*; D008875:Middle Aged; D009092:Mucous Membrane / Q000276:immunology* / Q000821:virology; D055815:Young Adult
chemical_list: D015703:Antigens, CD; D039001:Integrin alpha Chains; D007376:Interleukin-2; C091367:alpha E integrins