High expression of OX-40, ICOS, and low expression PD-L1 of follicular helper and follicular cytotoxic T cells in chronic lymphocytic leukemia

Chronic lymphocytic leukemia (CLL) is the most common leukemia in the elderly. T follicular helper (T FH ) and follicular cytotoxic T (T FC ) cells are a subset of CD4 + and CD8 + T cells expressing CXCR5, respectively. OX-40, ICOS, and PD-L1 are secondary immune checkpoint molecules and have a role in the maintenance of an immune response. The literature about the role of ICOS, OX-40, and PD-L1 receptors of T FH and, especially T FC cells, in CLL is limited. In this study, peripheral blood mononuclear cells (PBMCs) were isolated from heparinized blood samples by density gradient centrifugation using Ficoll-Paque from 34 CLL patients and 19 healthy subjects. The expression of ICOS, OX-40, and PD-L1 of T FC and T FH cells in CLL patients was investigated by flow cytometry. According to healthy subjects, T FH and T FC cell levels were increased in CLL patients. High-ICOS and low-PD-L1 expression in T FH cells and high OX-40 and ICOS, low-PD-L1 expression in T FC cells of CLL patients compared to healthy subjects. OX-40 expression was positively correlated with T FH and T FC cells levels [ R = 0.504, ( p = 0.002) and R = 0.316, ( p = 0.05)]. Additionally, OX-40 expression of T FH was positively correlated with ICOS expression [ R = 0.660, ( p < 0.001)] and PD-L1 expression [ R = 0.649, ( p < 0.001)]. OX-40L, ICOSL, and PD-L1 expression of B cells were elevated in CLL patients compared to healthy subjects. OX-40L expression of B cells was positively correlated with ICOSL expression [ R = 0.568, ( p = 0.0004)] and PD-L1 expression. Elevated CD4 + CXCR5 + T FH and CD8 + CXCR5 + T FC cells with high OX-40 and ICOS activator and low-PD-1L inhibitor receptor expression in CLL patients might have a role in the pathogenesis of CLL.