title: The effects of human herpesvirus 8 infection and interferon-gamma response in cutaneous lesions of Kaposi sarcoma differ among human immunodeficiency virus-infected and uninfected individuals.
abstract: BACKGROUND
  Kaposi sarcoma (KS) is associated with human herpesvirus 8 (HHV-8). The cutaneous immune response in this tumour is not well established and a better understanding is necessary.
  
  
  OBJECTIVE
  To evaluate the HHV-8 expression and immune response in cutaneous lesions of classic KS (CKS) and AIDS-associated KS (AIDS-KS).
  
  
  METHODS
  We performed a quantitative immunohistochemical study of cells expressing HHV-8 latency-associated nuclear antigen (LANA), CD4, CD8 and interferon (IFN)-gamma in skin lesions from patients with CKS and AIDS-KS (with or without highly active antiretroviral therapy, HAART).
  
  
  RESULTS
  CKS showed higher LANA expression compared with AIDS-KS, regardless of HAART. We also found higher LANA expression in nodules compared with patch/plaque lesions. The tissue CD4+ cell proportion was lower in AIDS-KS patients without HAART than in patients with CKS. In CKS lesions, CD4+ and CD8+ cells expressed IFN-gamma, as shown by double immunostaining. AIDS-KS presented low numbers of IFN-gamma-expressing cells. CD8+ cell numbers were similar in all groups, which appeared unrelated to the clinical or epidemiological type of KS.
  
  
  CONCLUSIONS
  Our quantitative data on the pattern of KS lesions in selected groups of patients, as shown by in situ immune response, demonstrated a CD4+ T-cell involvement associated with IFN-gamma, an environment of immune response-modified human immunodeficiency virus (HIV) infection. In our sample, the promotion of KS in patients without HIV appears to be related to higher HHV-8 load or virulence than in those with AIDS. This higher resistance may be explained by a sustained immune response against this herpesvirus, that is only partially restored but effective after HAART.
authors.affiliation: Department of Pathology, Faculty of Medical Sciences, University of São Paulo, São Paulo 01246-903, Brazil. fernandaguedes@usp.br
authors.forename: F
authors.initials: F
authors.lastname: Guedes
authors.forename: H F
authors.initials: HF
authors.lastname: de Andrade
authors.forename: E R
authors.initials: ER
authors.lastname: Fernandes
authors.forename: F F
authors.initials: FF
authors.lastname: Tuon
authors.forename: R A
authors.initials: RA
authors.lastname: Brasil
authors.forename: C
authors.initials: C
authors.lastname: Pagliari
authors.forename: M I S
authors.initials: MI
authors.lastname: Duarte
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000276:immunology* / Q000821:virology; D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000276:immunology; D000368:Aged; D000369:Aged, 80 and over; D000956:Antigens, Viral / Q000378:metabolism; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D019288:Herpesvirus 8, Human / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000378:metabolism; D012514:Sarcoma, Kaposi / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D012878:Skin Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000821:virology
chemical_list: D000956:Antigens, Viral; D009687:Nuclear Proteins; C109540:latency-associated nuclear antigen; D007371:Interferon-gamma