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

Br J Dermatol. 2008 Sep;159(4):839-46. doi: 10.1111/j.1365-2133.2008.08755.x. Epub 2008 Jul 17.

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.

Objectives: 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.

MeSH terms

  • AIDS-Related Opportunistic Infections / immunology*
  • AIDS-Related Opportunistic Infections / virology
  • Acquired Immunodeficiency Syndrome / drug therapy
  • Acquired Immunodeficiency Syndrome / immunology
  • Aged
  • Aged, 80 and over
  • Antigens, Viral / metabolism
  • Antiretroviral Therapy, Highly Active
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Female
  • Herpesvirus 8, Human / immunology*
  • Humans
  • Immunity, Cellular
  • Interferon-gamma / metabolism
  • Male
  • Middle Aged
  • Nuclear Proteins / metabolism
  • Sarcoma, Kaposi / drug therapy
  • Sarcoma, Kaposi / immunology*
  • Sarcoma, Kaposi / virology
  • Skin Neoplasms / drug therapy
  • Skin Neoplasms / immunology*
  • Skin Neoplasms / virology

Substances

  • Antigens, Viral
  • Nuclear Proteins
  • latency-associated nuclear antigen
  • Interferon-gamma