title: CCR5 expression is elevated on endocervical CD4+ T cells in healthy postmenopausal women.
abstract: BACKGROUND
  New HIV-1 infections are increasing in older American women largely through heterosexual transmission. Activated CD4+ T cells and CCR5 expression are linked to HIV-1 susceptibility, but whether these parameters are altered in the cervix of older women is unknown.
  
  
  METHODS
  Whole blood and in some instances endocervical brush samples were collected from healthy premenopausal (n = 22) and postmenopausal women (n = 24). Percentages of HLA-DR(DR)+CD38(38)+CD4+ T cells and HIV-1 chemokine coreceptor expression were determined by flow cytometry.
  
  
  RESULTS
  Percentages of DR+38+CD4+ T cells were 6 times greater in cervix (median: 6.4%) than blood (median: 1.1%; P < 0.001) but did not differ within each compartment between premenopausal and postmenopausal women (P = 0.2). Postmenopausal women had greater percentages of CCR5+CD4+ and CCR5+DR+38+CD4+ T cells compared with premenopausal women in cervix (median: 70% vs. 42%, P = 0.005; and 80% vs. 57%; P = 0.05, respectively) and blood (medians: 22% vs. 13%, and 76% vs. 62%, respectively; P < 0.001). Postmenopausal women had more CCR5 molecules on cervical DR+38+CD4+ T cells (median: 3176) than premenopausal women (median: 1776; P = 0.02). Age and percent CCR5+CD4+ and CCR5+DR+38+CD4+ cells were linearly related in cervix (r(2) = 0.47, P < 0.001 and r(2) = 0.25, P = 0.01, respectively) and blood (r(2) = 0.20, P = 0.001 and r(2) = 0.31, P < 0.001; respectively), but confounding of age with menopause could not be excluded. Cervical CXCR4 expression did not differ substantially between premenopausal and postmenopausal women.
  
  
  CONCLUSIONS
  Elevated cervical CCR5 expression in postmenopausal women may increase their risk for HIV-1 acquisition. Studies are needed to confirm whether elevated CCR5 expression confers increased HIV-1 susceptibility in postmenopausal women, and if it is related to hormonal or nonhormonal effects of aging.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of Colorado Denver, Aurora, CO 80045, USA. amie.meditz@ucdenver.edu
authors.forename: Amie L
authors.initials: AL
authors.lastname: Meditz
authors.forename: Kerrie L
authors.initials: KL
authors.lastname: Moreau
authors.forename: Samantha
authors.initials: S
authors.lastname: MaWhinney
authors.forename: Wendolyn S
authors.initials: WS
authors.lastname: Gozansky
authors.forename: Kelsey
authors.initials: K
authors.lastname: Melander
authors.forename: Wendy M
authors.initials: WM
authors.lastname: Kohrt
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Wierman
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Connick
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000097:blood / Q000276:immunology; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002584:Cervix Uteri / Q000166:cytology / Q000276:immunology*; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004198:Disease Susceptibility / Q000276:immunology; D005260:Female; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006684:HLA-DR Antigens / Q000097:blood / Q000276:immunology; D006801:Humans; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D017698:Postmenopause / Q000097:blood / Q000276:immunology*; D019713:Receptors, CCR5 / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics / Q000276:immunology; D018709:Statistics, Nonparametric
chemical_list: D006684:HLA-DR Antigens; D019713:Receptors, CCR5; D004247:DNA; D051997:ADP-ribosyl Cyclase 1
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