title: Dysregulated immunophenotypic attributes of plasmacytoid but not myeloid dendritic cells in HIV-1 infected individuals in the absence of highly active anti-retroviral therapy.
abstract: Dendritic cells (DC) in HIV-1-infected individuals are decreased and their dysfunction has been implicated in HIV-1 immunopathogenesis. The mechanism of their dysfunction remains unclear, thus we analysed the expression of membrane molecules associated with immune regulation and DC activation in myeloid (mDC) and plasmacytoid DC (pDC) in therapy-naive and highly active anti-retroviral therapy (HAART)-treated HIV-1(+)  patients. DC from healthy controls, untreated HIV-1(+)  and HAART-treated patients were assessed by flow cytometry for expression of: anergy and apoptosis inducing molecules [programmed death (PD)-1 and its ligands PD-L1 and PD-L2], inhibitory and regulatory T cell-inducing molecules [immunoglobulin-like transcript (ILT)-3 and ILT-4], interferon (IFN)-α inhibitory receptor (ILT-7) and co-stimulatory molecules (CD80, CD83, and CD86). pDC from untreated HIV-1(+)  patients expressed significantly lower levels of ILT-7 compared to healthy controls, while HAART-treated patients showed normal expression. pDC were also found to express moderately higher levels of PD-L1 and ILT-3 and lower levels of PD-L2 receptors in untreated patients compared to controls and HAART-treated patients. No significant changes were observed in mDC. There were no associations between the percentages and levels of expression of these molecules by pDC and viral load or CD4 T cell count. In conclusion, pDC but not mDC from HIV-1(+)  patients with active viraemia display higher levels of apoptosis and T regulatory-inducing molecules and may be predisposed to chronically produce IFN-α through down-regulation of ILT-7. HAART restored normal expression levels of these receptors.
authors.affiliation: Department of Immunology, Imperial College London, Chelsea and Westminster Hospital, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Benlahrech
authors.forename: A
authors.initials: A
authors.lastname: Yasmin
authors.forename: S J
authors.initials: SJ
authors.lastname: Westrop
authors.forename: A
authors.initials: A
authors.lastname: Coleman
authors.forename: A
authors.initials: A
authors.lastname: Herasimtschuk
authors.forename: E
authors.initials: E
authors.lastname: Page
authors.forename: P
authors.initials: P
authors.lastname: Kelleher
authors.forename: F
authors.initials: F
authors.lastname: Gotch
authors.forename: N
authors.initials: N
authors.lastname: Imami
authors.forename: S
authors.initials: S
authors.lastname: Patterson
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D060890:B7-H1 Antigen / Q000276:immunology / Q000378:metabolism; D015331:Cohort Studies; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D022423:Myeloid Cells / Q000276:immunology* / Q000378:metabolism; D061026:Programmed Cell Death 1 Receptor / Q000276:immunology / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000276:immunology / Q000378:metabolism; D011971:Receptors, Immunologic / Q000276:immunology / Q000378:metabolism; D014766:Viremia / Q000276:immunology / Q000378:metabolism; D055815:Young Adult
chemical_list: D015703:Antigens, CD; D060890:B7-H1 Antigen; C423236:CD274 protein, human; C488262:LILRA4 protein, human; C491341:LILRB2 protein, human; C107907:LILRB4 protein, human; D008562:Membrane Glycoproteins; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic