title: Increased interferon alpha expression in circulating plasmacytoid dendritic cells of HIV-1-infected patients.
abstract: BACKGROUND
  The role of plasmacytoid dendritic cells (pDC) and interferon alpha (IFN alpha) in HIV-1 infection is still unclear. On one hand, HIV-1 disease is associated with a progressive decline of pDC, which displays reduced ability to produce IFN alpha after in vitro challenge. On the other hand, high IFN alpha serum levels in HIV-1-infected individuals have been proposed to promote immune hyper-activation and disease progression.
  
  
  METHODS
  We sought to determine whether disappearance of pDC in HIV-1 disease is due to homing in lymphoid tissues. We also studied IFN alpha and myxovirus resistance protein A (MxA) expression in unstimulated pDC and correlated these results with selected clinical and laboratory parameters.
  
  
  RESULTS
  We found that pDC decline markedly in peripheral blood of patients progressing to disease but at the same time express much higher levels of IFN alpha and MxA compared to control individuals. On the other hand, we observed steady pDC counts in lymph nodes of HIV-1 patients. The frequency of circulating pDC correlated directly with CD4 cell counts and inversely with viral load. However, we found no correlation between IFN alpha and MxA expression levels, CD4 counts, and viral load.
  
  
  CONCLUSIONS
  Circulating pDC decline sharply in the course of HIV-1 disease, but express high levels of IFN alpha, which may represent a hallmark of systemic immune dysfunction.
authors.affiliation: First Department of Internal Medicine, University of Cologne, Cologne, Germany.
authors.forename: Clara
authors.initials: C
authors.lastname: Lehmann
authors.forename: Jill M
authors.initials: JM
authors.lastname: Harper
authors.forename: Dirk
authors.initials: D
authors.lastname: Taubert
authors.forename: Pia
authors.initials: P
authors.lastname: Hartmann
authors.forename: Gerd
authors.initials: G
authors.lastname: Fätkenheuer
authors.forename: Norma
authors.initials: N
authors.lastname: Jung
authors.forename: Jan
authors.initials: J
authors.lastname: van Lunzen
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Stellbrink
authors.forename: Robert C
authors.initials: RC
authors.lastname: Gallo
authors.forename: Fabio
authors.initials: F
authors.lastname: Romerio
mesh_terms: D000328:Adult; D000368:Aged; D000954:Antigens, Surface / Q000378:metabolism; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D003713:Dendritic Cells / Q000378:metabolism* / Q000821:virology; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D015497:HIV-1; D006801:Humans; D016898:Interferon-alpha / Q000097:blood*; D053650:Interleukin-3 Receptor alpha Subunit / Q000378:metabolism; D037181:Lectins, C-Type / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000821:virology; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged; D064547:Myxovirus Resistance Proteins; D011971:Receptors, Immunologic / Q000378:metabolism; D016185:Receptors, Interleukin-3 / Q000378:metabolism; D019562:Viral Load
chemical_list: D000954:Antigens, Surface; C443299:CLEC4C protein, human; C115022:IL3RA protein, human; D016898:Interferon-alpha; D053650:Interleukin-3 Receptor alpha Subunit; D037181:Lectins, C-Type; C579071:MX1 protein, human; D008562:Membrane Glycoproteins; D064547:Myxovirus Resistance Proteins; D011971:Receptors, Immunologic; D016185:Receptors, Interleukin-3; C478196:blood dendritic cell antigen 4, human; D019204:GTP-Binding Proteins