title: Effects of depot-medroxyprogesterone acetate on the immune microenvironment of the human cervix and endometrium: implications for HIV susceptibility.
abstract: Depot-medroxyprogesterone acetate is a commonly used injectable contraceptive that has been associated with an increased risk of HIV acquisition. This study compares effects of depot-medroxyprogesterone acetate on immune parameters from several upper reproductive tract compartments relevant to HIV-1 susceptibility in repetitive samples from 15 depot-medroxyprogesterone acetate users and 27 women not on hormonal contraceptives. Compared with samples from unexposed women in the mid-luteal phase, depot-medroxyprogesterone acetate use was associated with: increased endocervical concentrations of MCP1 and IFNalpha2; decreased endocervical concentrations of IL1beta and IL6; increased proportions of endometrial CD4+ and CD8+ cells expressing the activation marker HLADR; increased density of endometrial macrophages; and decreased density of endometrial regulatory T cells. Unlike previous reports with samples from the vagina, we did not observe increased expression of the HIV co-receptor CCR5 on CD4+ T cells in the endocervix or endometrium. Our results indicate important differences in anatomic compartments regarding mechanisms by which depot-medroxyprogesterone acetate could be associated with increased risk of HIV acquisition, including increased recruitment of macrophages to the endometrium, decreased levels of pro-inflammatory cytokines in the endocervix possibly leading to enhanced susceptibility to viral infection, and activation of endometrial T cells.
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, California, USA.
authors.forename: K K
authors.initials: KK
authors.lastname: Smith-McCune
authors.affiliation: Department of Epidemiology and Biostatistics, University of California, San Francisco, California, USA.
authors.forename: J F
authors.initials: JF
authors.lastname: Hilton
authors.affiliation: Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, California, USA.
authors.forename: U
authors.initials: U
authors.lastname: Shanmugasundaram
authors.affiliation: Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, California, USA.
authors.forename: J W
authors.initials: JW
authors.lastname: Critchfield
authors.affiliation: Department of Epidemiology and Biostatistics, University of California, San Francisco, California, USA.|Departments of Clinical Pharmacy and Medicine, University of California, San Francisco, California, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: Greenblatt
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, California, USA.
authors.forename: D
authors.initials: D
authors.lastname: Seidman
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, California, USA.
authors.forename: S
authors.initials: S
authors.lastname: Averbach
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, California, USA.
authors.forename: L C
authors.initials: LC
authors.lastname: Giudice
authors.affiliation: Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, California, USA.
authors.forename: B L
authors.initials: BL
authors.lastname: Shacklett
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D060833:Cellular Microenvironment; D002584:Cervix Uteri / Q000276:immunology*; D018932:Chemokine CCL2 / Q000378:metabolism; D003270:Contraceptive Agents / Q000627:therapeutic use*; D003692:Delayed-Action Preparations; D004198:Disease Susceptibility; D004717:Endometrium / Q000276:immunology*; D005260:Female; D015658:HIV Infections / Q000276:immunology; D006801:Humans; D016898:Interferon-alpha / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D017258:Medroxyprogesterone Acetate / Q000627:therapeutic use*; D019713:Receptors, CCR5 / Q000378:metabolism; D055815:Young Adult
chemical_list: C111835:CCL2 protein, human; C584933:CCR5 protein, human; D018932:Chemokine CCL2; D003270:Contraceptive Agents; D003692:Delayed-Action Preparations; D016898:Interferon-alpha; D053583:Interleukin-1beta; D015850:Interleukin-6; D019713:Receptors, CCR5; D017258:Medroxyprogesterone Acetate