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. 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.