title: Impact of TNFalpha, LTalpha, Fc gammaRII and complement receptor on HIV-1 trapping in lymphoid tissue from HIV-infected patients.
abstract: OBJECTIVE
  To investigate HIV trapping mechanisms in patients with acute infection and in asymptomatic individuals prior to and during antiretroviral therapy. To determine the role of complement receptor (CR), Fc gamma receptor II (Fc gammaRII), tumour necrosis factor alpha (TNFalpha), and lymphotoxin alpha (LTalpha) expression in HIV trapping efficiency.
  
  
  METHODS
  Lymphoid tissues from three acutely HIV-infected patients and six asymptomatic, chronically HIV-infected patients collected prior to and during antiretroviral therapy were compared with lymphoid tissues from six HIV-seronegative subjects. HIV, TNFalpha and LTalpha RNA expression was detected and quantified by fluorescence in situ hybridization. CR, Fc gammaRII and HIV p24 antigen were detected and quantified by fluorescence immunohistochemistry.
  
  
  RESULTS
  The amount of trapped HIV did not differ significantly between patients with acute HIV infection and asymptomatic individuals, and was independent of the presence of CR or Fc gammaRII expression. However, in patients with acute infection, the amount of trapped virus was correlated inversely with the number of HIV-infected cells (P = 0.0092) and with the size of the light zone (P = 0.037). In these patients, the number of TNFalpha-expressing cells was correlated inversely with the amount of trapped virus (P = 0.014) and positively correlated with the size of the light zone in germinal centers (P = 0.041). No correlations were observed between TNFalpha or LTalpha expression and Fc gammaRII or CR expression.
  
  
  CONCLUSIONS
  This report provides the first evidence that in humans TNFalpha is involved in the development of lymphoid follicles, HIV trapping, and, consequently, in early host immune responses. A model is proposed for early events in patients during acute HIV infection.
authors: Department of Internal Medicine, University Hospital Zurich, Switzerland.
authors: M C
authors: MC
authors: Knuchel
authors: R F
authors: RF
authors: Speck
authors: E
authors: E
authors: Schlaepfer
authors: H
authors: H
authors: Kuster
authors: P
authors: P
authors: Ott
authors: H F
authors: HF
authors: Günthard
authors: M
authors: M
authors: Opravil
authors: R W
authors: RW
authors: Cone
authors: R
authors: R
authors: Weber
mesh_terms: D000208:Acute Disease; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D015153:Blotting, Western; D002908:Chronic Disease; D018858:Germinal Center / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000821:virology; D015483:HIV Antibodies / Q000096:biosynthesis / Q000276:immunology; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology*; D006679:HIV Seropositivity / Q000188:drug therapy / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008221:Lymphoid Tissue / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D008233:Lymphotoxin-alpha / Q000235:genetics / Q000502:physiology*; D018448:Models, Immunological; D012367:RNA, Viral / Q000032:analysis / Q000235:genetics; D011951:Receptors, Complement / Q000378:metabolism*; D017452:Receptors, IgG / Q000096:biosynthesis / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000502:physiology*; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D015483:HIV Antibodies; D008233:Lymphotoxin-alpha; D012367:RNA, Viral; D011951:Receptors, Complement; D017452:Receptors, IgG; D014409:Tumor Necrosis Factor-alpha