title: Progesterone Levels Associate with a Novel Population of CCR5+CD38+ CD4 T Cells Resident in the Genital Mucosa with Lymphoid Trafficking Potential.
abstract: The female genital tract (FGT) provides a means of entry to pathogens, including HIV, yet immune cell populations at this barrier between host and environment are not well defined. We initiated a study of healthy women to characterize resident T cell populations in the lower FGT from lavage and patient-matched peripheral blood to investigate potential mechanisms of HIV sexual transmission. Surprisingly, we observed FGT CD4 T cell populations were primarily CCR7(hi), consistent with a central memory or recirculating memory T cell phenotype. In addition, roughly half of these CCR7(hi) CD4 T cells expressed CD69, consistent with resident memory T cells, whereas the remaining CCR7(hi) CD4 T cells lacked CD69 expression, consistent with recirculating memory CD4 T cells that traffic between peripheral tissues and lymphoid sites. HIV susceptibility markers CCR5 and CD38 were increased on FGT CCR7(hi) CD4 T cells compared with blood, yet migration to the lymphoid homing chemokines CCL19 and CCL21 was maintained. Infection with GFP-HIV showed that FGT CCR7(hi) memory CD4 T cells are susceptible HIV targets, and productive infection of CCR7(hi) memory T cells did not alter chemotaxis to CCL19 and CCL21. Variations of resident CCR7(hi) FGT CD4 T cell populations were detected during the luteal phase of the menstrual cycle, and longitudinal analysis showed the frequency of this population positively correlated to progesterone levels. These data provide evidence women may acquire HIV through local infection of migratory CCR7(hi) CD4 T cells, and progesterone levels predict opportunities for HIV to access these novel target cells.
authors.affiliation: Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30329;
authors.forename: Alison
authors.identifier: 0000-0001-6508-0038
authors.initials: A
authors.lastname: Swaims-Kohlmeier
authors.affiliation: Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30329;
authors.forename: Richard E
authors.initials: RE
authors.lastname: Haaland
authors.affiliation: Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, GA 30322;
authors.forename: Lisa B
authors.identifier: 0000-0002-6668-6389
authors.initials: LB
authors.lastname: Haddad
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322;
authors.forename: Anandi N
authors.identifier: 0000-0002-6305-2727
authors.initials: AN
authors.lastname: Sheth
authors.affiliation: Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30329;
authors.forename: Tammy
authors.initials: T
authors.lastname: Evans-Strickfaden
authors.affiliation: Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30329;
authors.forename: L Davis
authors.initials: LD
authors.lastname: Lupo
authors.affiliation: Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, GA 30322;
authors.forename: Sarah
authors.identifier: 0000-0002-3875-425X
authors.initials: S
authors.lastname: Cordes
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322;
authors.forename: Alfredo J
authors.initials: AJ
authors.lastname: Aguirre
authors.affiliation: Division of STD Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30329; and.
authors.forename: Kathryn A
authors.identifier: 0000-0001-6766-1522
authors.initials: KA
authors.lastname: Lupoli
authors.affiliation: Division of STD Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30329; and.
authors.forename: Cheng-Yen
authors.initials: CY
authors.lastname: Chen
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322;
authors.forename: Igho
authors.identifier: 0000-0003-2735-1903
authors.initials: I
authors.lastname: Ofotukun
authors.affiliation: Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30329;
authors.forename: Clyde E
authors.initials: CE
authors.lastname: Hart
authors.affiliation: Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322 jkohlmeier@emory.edu.
authors.forename: Jacob E
authors.initials: JE
authors.lastname: Kohlmeier
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D002478:Cells, Cultured; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D002633:Chemotaxis; D018562:Disease Transmission, Infectious; D005260:Female; D005836:Genitalia, Female / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D008597:Menstrual Cycle; D011374:Progesterone / Q000378:metabolism*; D019713:Receptors, CCR5 / Q000378:metabolism; D054400:Receptors, CCR7 / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000821:virology
chemical_list: D015415:Biomarkers; C584933:CCR5 protein, human; C515370:CCR7 protein, human; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D019713:Receptors, CCR5; D054400:Receptors, CCR7; D011374:Progesterone; D051997:ADP-ribosyl Cyclase 1