Low T cell responses to human herpesvirus 8 in patients with AIDS-related and classic Kaposi sarcoma

Background. Kaposi sarcoma (KS) occurs mainly in immunocompromised patients and is strongly associated with infection with human herpesvirus 8 (HHV-8; also known as "KS-associated herpesvirus"). We hypothesized that KS is linked to deficiencies in specific anti-HHV-8 T cell immunity. Methods. We studied asymptomatic HHV-8 carriers coinfected with human immunodeficiency virus (HIV; n = 23) and patients with HIV-related or classic KS (n = 29). We used an interferon-gamma enzyme-linked immunospot assay with 56 specific peptides distributed on 6 HHV-8 proteins (glycoprotein [gp] B, gpH, gp35/37, latent nuclear antigen 1 [LANA-1], K12, and K15) to detect HHV-8-specific T cell responses. Results. We found that patients with KS responded to these peptides less often and had much lower HHV-8 8-specific T cells counts than did asymptomatic HHV-8 carriers (P = .001 and P = .004, respectively), regardless of CD4 T cell count or HHV-8 load. The frequency of Epstein-Barr virus-specific T cells was similar in both groups. Conclusions. Our results suggest that HIV-related and classic KS are associated with a lack of HHV-8-specific T cells. Also, we have described 8 new HHV-8 T cell epitopes in LANA-1, K12, and K15, including 2 CD4 T cell epitopes. These data provide new insight into HHV-8 cellular immunity.