title: Robust interferon-α and IL-12 responses by dendritic cells are related to efficient CD4+ T-cell recovery in HIV patients on ART.
abstract: Amongst HIV patients with successful virological responses to antiretroviral therapy (ART), poor CD4(+) T-cell recovery is associated with low nadir CD4(+) T-cell counts and persistent immune activation. These factors might be influenced by dendritic cell (DC) function. Interferon-α-producing plasmacytoid DC and IL-12-producing myeloid DC were quantified by flow cytometry after stimulation with agonists to TLR7/8 (CL075) or TLR9 (CpG-ODN). These were compared between patients who achieved CD4(+) T-cell counts above or below 200 cells/μL after 6 months on ART (High vs. Low groups). High Group patients had more DC producing interferon-α or IL-12 at Weeks 6 and 12 on ART than Low Group patients. The frequencies of cytokine-producing DC at Week 12 were directly correlated with CD4(+) T-cell counts at baseline and at Week 12. Patients with good recovery of CD4(+) T-cells had robust TLR-mediated interferon-α responses by plasmacytoid DC and IL-12 responses by myeloid DC during early ART (1-3 months).
authors.affiliation: School of Pathology and Laboratory Medicine, University of Western Australia, Nedlands, Australia. dtan@meddent.uwa.edu.au
authors.forename: Dino Bee Aik
authors.initials: DB
authors.lastname: Tan
authors.forename: Yean Kong
authors.initials: YK
authors.lastname: Yong
authors.forename: Andrew
authors.initials: A
authors.lastname: Lim
authors.forename: Hong Yien
authors.initials: HY
authors.lastname: Tan
authors.forename: Adeeba
authors.initials: A
authors.lastname: Kamarulzaman
authors.forename: Martyn
authors.initials: M
authors.lastname: French
authors.forename: Patricia
authors.initials: P
authors.lastname: Price
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism; D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D015658:HIV Infections / Q000188:drug therapy* / Q000473:pathology*; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D016898:Interferon-alpha / Q000378:metabolism*; D018664:Interleukin-12 / Q000378:metabolism*; D007958:Leukocyte Count; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D051199:Toll-Like Receptor 7 / Q000819:agonists; D051200:Toll-Like Receptor 8 / Q000819:agonists; D051217:Toll-Like Receptor 9 / Q000819:agonists
chemical_list: D044966:Anti-Retroviral Agents; C551788:CL 075; C408982:CPG-oligonucleotide; D006684:HLA-DR Antigens; D016898:Interferon-alpha; D008562:Membrane Glycoproteins; D009838:Oligodeoxyribonucleotides; D011804:Quinolines; C495348:TLR7 protein, human; C495349:TLR8 protein, human; C495371:TLR9 protein, human; D013844:Thiazoles; D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8; D051217:Toll-Like Receptor 9; D018664:Interleukin-12; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1