title: Loss of Th22 cells is associated with increased immune activation and IDO-1 activity in HIV-1 infection.
abstract: BACKGROUND
  Immune activation plays a key role in the immunopathogenesis of HIV-1 infection. Microbial translocation, secondary to loss of epithelial integrity and mucosal immune deficiency, is believed to contribute to systemic immune activation. Interleukin 22 maintains intestinal epithelial barrier integrity and stimulates the secretion of antimicrobial peptides that limit bacterial dissemination and intestinal inflammation. Interleukin 22 is secreted by CD4 T-helper (Th)22 cells independently of interleukin 17A and interferon γ. Th22 cells are characterized by the expression of chemokine receptors (CCR)4, CCR6, and CCR10.
  
  
  METHODS
  We analyzed the frequency of Th22, Th17, Th1, and CD4 T regulatory (Treg) cells, markers of immune activation (expression of CD38 on CD8 T cells, neopterin, soluble CD14), microbial translocation (lipopolysaccharide-binding protein and 16s ribosomal DNA), and indoleamine 2,3-dioxygenase 1 activity in peripheral blood of antiretroviral therapy (ART)-experienced and ART-naive HIV-1-infected patients and healthy controls.
  
  
  RESULTS
  We showed a significant reduction in the frequency of Th22 cells in HIV ART-naive patients compared with the healthy controls and HIV ART-experienced patients. We observed a shift away from Th22 and Th17 to Treg cells, which was partially reversed by effective ART. Markers of immune activation negatively correlated with Th22 and Th17 proportions, and with Th22:Treg and Th17:Treg ratios in ART-naive patients. Increased indoleamine 2,3-dioxygenase 1 activity negatively correlated with Th22:Treg and Th17:Treg ratios in the ART-naive group.
  
  
  CONCLUSIONS
  Loss of Th22 cells and disruption in the balance of Th22 and Treg cells may contribute toward systemic immune activation and mucosal immune deficiency during HIV-1 infection.
authors.affiliation: *Department of Medicine, Imperial College, London, United Kingdom; †Division of Biological Chemistry, Biocenter, Medical University, Innsbruk, Austria; ‡Department of Infection and Immunity, Imperial College NHS Trust, London, United Kingdom; and §Department of HIV and Sexual Health, Chelsea and Westminster Hospital NHS Foundation Trust, London, United Kingdom.
authors.forename: Emma E
authors.initials: EE
authors.lastname: Page
authors.forename: Louise
authors.initials: L
authors.lastname: Greathead
authors.forename: Rebecca
authors.initials: R
authors.lastname: Metcalf
authors.forename: Sally-Ann
authors.initials: SA
authors.lastname: Clark
authors.forename: Melanie
authors.initials: M
authors.lastname: Hart
authors.forename: Dietmar
authors.initials: D
authors.lastname: Fuchs
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Pantelidis
authors.forename: Frances
authors.initials: F
authors.lastname: Gotch
authors.forename: Anton
authors.initials: A
authors.lastname: Pozniak
authors.forename: Mark
authors.initials: M
authors.lastname: Nelson
authors.forename: Adriano
authors.initials: A
authors.lastname: Boasso
authors.forename: Brian
authors.initials: B
authors.lastname: Gazzard
authors.forename: Peter
authors.initials: P
authors.lastname: Kelleher
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism; D000328:Adult; D018988:Bacterial Translocation; D015415:Biomarkers / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism*; D007378:Interleukins / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D019798:Neopterin / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism; D000097043:Interleukin-22
chemical_list: D051997:ADP-ribosyl Cyclase 1; D015415:Biomarkers; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007378:Interleukins; D018950:Lipopolysaccharide Receptors; D019798:Neopterin; D000097043:Interleukin-22; C576710:IDO1 protein, human