CD4+ and CD8+ T-Cell Skewness in Classic Kaposi Sarcoma

It is widely accepted that a deranged immune system plays a key role in the onset and evolution of classic Kaposi
sarcoma (CKS). Nevertheless, the usage of the T-cell receptor (TCR) β-variable (BV) chain repertoire expressed by
peripheral blood lymphocytes in patients with CKS is still unknown. With the aim of providing some further insights
into the complex role of the immune system in CKS pathogenesis, we performed an extensive analysis of the TCR
BV repertoire in both CD4+ and CD8+ T cells in 30 human herpesvirus 8–positive Sardinian patients with CKS and an
equal number of age-matched healthy controls. We used a panel of monoclonal antibodies covering approximately
70% of human BV subfamilies and third complementarity determining region (CDR3) spectratyping. Patients with
CKS showed an increased frequency of BV expansions in both CD4+ and CD8+ lymphocytes, with no prevalent
clones. On spectratyping analysis, most of the 720 BV CDR3 profiles obtained from both CD4+ and CD8+ T cells
in patients with CKS were skewed. In particular, the surprising increase of BV skewing observed in CD4+ lymphocytes
mimics the pattern of progressive TCR BV narrowing described in responses to persistent viral antigen stimulations.
Our findings support the hypothesis that CKS evolution is associated with inadequate activation rather than
impairment of the immune system.