title: Impact of antigen specificity on CD4+ T cell activation in chronic HIV-1 infection.
abstract: BACKGROUND
  HIV infection induces chronic immune activation which is associated with accelerated disease progression; the causes of this activation, however, are incompletely understood. We investigated the activation status of CD4+ T cells specific for chronic herpes viruses and the non-persistent antigen tetanus toxoid (TT) in HIV positive and HIV negative donors to assess whether persistent infections contribute to chronic CD4+ T cell activation.
  
  
  METHODS
  Untreated HIV+ patients and healthy, aged matched controls were recruited and activation levels assessed and compared between cells specific for persistent and non-persistent antigens. Activation levels on antigen-specific CD4+ T cells were measured by intracellular cytokine staining following in vitro stimulation with various recall antigens (CMV, EBV, HSV, VZV and TT) in conjunction with cell surface phenotyping.
  
  
  RESULTS
  Activation levels of herpes virus-specific CD4+ T cell populations, assessed by co-expression of CD38 and HLA-DR, were significantly elevated in HIV+ individuals compared to normal controls and compared to TT-specific responses. In contrast, we found similar levels of activation of TT-specific CD4+ T cells in HIV+ and HIV- donors.
  
  
  CONCLUSIONS
  These results show a disparate distribution of immune activation within CD4+ T cell populations depending on their specificity and suggest that the elevated level of immune activation that characterizes chronic HIV infection may be influenced by the persistence of other antigens.
authors: Institute of Microbiology, Swiss Federal Institute of Technology (ETH) Zurich, Zurich, Switzerland.
authors: Miranda Z
authors: MZ
authors: Smith
authors: Sonia
authors: S
authors: Bastidas
authors: Urs
authors: U
authors: Karrer
authors: Annette
authors: A
authors: Oxenius
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000276:immunology; D000328:Adult; D018138:Alphaherpesvirinae / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D002908:Chronic Disease; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000276:immunology*; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D039641:Integrin beta Chains / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology; D008875:Middle Aged; D061026:Programmed Cell Death 1 Receptor / Q000276:immunology
chemical_list: D000956:Antigens, Viral; D006684:HLA-DR Antigens; D039641:Integrin beta Chains; D008562:Membrane Glycoproteins; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; C091368:integrin beta7; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1