title: Early HIV-1 infection is associated with reduced frequencies of cervical Th17 cells.
abstract: BACKGROUND
  The hallmark of HIV infection is progressive but variable rates of systemic and mucosal CD4 depletion, leading to immunodeficiency. The impact of early HIV infection on cervical CD4 T-cell populations in humans remains poorly described.
  
  
  METHODS
  We analyzed cytobrush-derived immune cells by flow cytometry and cytokines in cervicovaginal lavage from participants in early HIV (<6 months postinfection), chronic HIV, and HIV-uninfected controls.
  
  
  RESULTS
  CD4:CD8 ratios declined rapidly in both the cervix and the blood following HIV infection. In contrast, absolute cervical CD4 T-cell counts in early HIV were comparable to HIV-uninfected participants, declining only in chronic infection. Early HIV infection was associated with increases in RANTES and MIP3a in cervicovaginal fluids. Concurrently, slight increases in activated cells (CD38HLA-DR) and higher levels of CTLA4 expression on Tregs in the cervix were observed. Although study groups did not differ with respect to levels of CCR5, integrin B7, or CD69, the frequencies of Th17 cells (defined as CCR6CCR10) was reduced by >10-fold in early HIV infection and Th1 cells (defined as CCR6CXCR3) were reduced by >2-fold. Although CCR6CCR10 cells did not differ in HIV receptor expression, these cells produced higher levels of interferon gamma and interleukin 17.
  
  
  CONCLUSIONS
  These data support the model of initial CD4 T-cell depletion followed by overall T-cell influx in response to infection and concomitant increases in immune activation, inflammation, and regulatory markers. These data are among the earliest characterization of the cellular milieu in the female genital tract following male-to-female HIV transmission.
authors.affiliation: *Department of Medical Microbiology, University of Nairobi, Nairobi, Kenya; †Department of Medicine, University of Toronto, Toronto, Ontario, Canada; ‡Centre for the AIDS Program of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban, South Africa; §Department of Obstetrics, Kenyatta National Hospital, Nairobi, Kenya; ‖Department of Epidemiology, University of North Carolina, Chapel Hill, NC; ¶Kenya AIDS Vaccine Initiative, Nairobi, Kenya; #Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada; and **University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Lyle R
authors.initials: LR
authors.lastname: McKinnon
authors.forename: Billy
authors.initials: B
authors.lastname: Nyanga
authors.forename: Connie J
authors.initials: CJ
authors.lastname: Kim
authors.forename: Preston
authors.initials: P
authors.lastname: Izulla
authors.forename: Jessie
authors.initials: J
authors.lastname: Kwatampora
authors.forename: Makobu
authors.initials: M
authors.lastname: Kimani
authors.forename: Kamnoosh
authors.initials: K
authors.lastname: Shahabi
authors.forename: Nelly
authors.initials: N
authors.lastname: Mugo
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Smith
authors.forename: A Omu
authors.initials: AO
authors.lastname: Anzala
authors.forename: Joshua
authors.initials: J
authors.lastname: Kimani
authors.forename: Rupert
authors.initials: R
authors.lastname: Kaul
mesh_terms: D000328:Adult; D016516:CD4-CD8 Ratio; D002460:Cell Line; D002584:Cervix Uteri / Q000276:immunology*; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D016130:Immunophenotyping; D019707:Receptors, Chemokine / Q000378:metabolism; D058504:Th17 Cells / Q000166:cytology*
chemical_list: D019707:Receptors, Chemokine