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

Abstract

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.

Azacitidine improves the T-cell repertoire in patients with myelodysplastic syndromes and acute myeloid leukemia with multilineage dysplasia

“…These findings were overall resembled by a different study, which also added that T-cell expansions were greater in bone marrow than in peripheral blood and were essentially sustained by CD8+CD57+CD28+ effector T-cells [32]. TCR repertoire abnormalities were also reported in the context of different hematologic [33,34] and extra-hematologic neoplastic disorders [35].…”

Derangement of the T‐cell repertoire in patients with B‐cell non‐Hodgkin's lymphoma

“…Whereas specific TCR repertoire patterns have now been demonstrated in different hematologic and extra‐hematologic malignancies , the few studies exploring the T‐cell compartment of patients with B‐cell NHL just point to an overall activation of the TCR repertoire and are extremely heterogeneous in terms of methodological approach and disease subtype . The only available spectratyping analysis was performed on unseparated peripheral T cells and showed a restricted TCR repertoire in marginal zone mucosa‐associated lymphoid tissue (MALT) NHL but not in other subtypes of indolent NHL, further corroborating the hypothesis of a superantigen stimulation in this specific histological entity .…”

Evidence of a skewed T‐cell repertoire in patients with light chain amyloidosis

“…The presence of a dominant peak with a relative intensity greater than 50% of the total peak area is usually used to specifically identify oligoclonal subfamilies (panel E) in the degree of CDR3 skewing in their T-cell repertoire involving both CD4+ and CD8+ cells. Altered TCR repertoire patterns have already been shown to characterize different malignancies [2][3][4][5] and to be potentially reversible after anti-neoplastic treatment [14]. In more details, a similar pattern has been recently demonstrated in patients with non Hodgkin lymphomas [3], while in different disorders, such as myelodysplastic syndromes, the increased degree of skewing was confined to the CD8+ subset [4].…”

“…The T-cell receptor (TCR) is one of the key molecules within the immunological synapse and the analysis of its repertoire offers a picture of both versatility and wideness of the whole immune T-cell compartment. Specific TCR repertoire patterns have been demonstrated in different hematologic [2][3][4] and extra-hematologic malignancies [5]. In particular, an overall activation of the T-cell compartment has been demonstrated in patients with multiple myeloma both on peripheral blood [6] and in peritumoral T-cells [7].…”