The role of CD40L-expressing CXCR5+CD8+ follicular cytotoxic T cells in chronic lymphocytic leukemia.

A newly identified cell subset within CD8⁺ T cells expressing CXCR5 of follicular cytotoxic T cells (T_FC) lyse the infected or tumor cells. Recent studies have suggested that some T_FC cell subsets may be involved in the regulation of antibody responses. We aimed to determine the subset of T_FC which differentiates in patients diagnosed with chronic lymphocytic leukemia (CLL) and their role in CLL immunopathogenesis. The peripheral blood mononuclear cells were isolated from 29 CLL patients and 19 healthy subjects. Intracellular IL-4, IL-17, IL-21, IFN-γ, perforin, and granzyme-B levels were investigated in T_FC subsets. Increased levels of IL-4, IL-17, IL-21, IFN-γ and perforin, and decreased granzyme B expression levels were observed in CD40L⁺ T_FC cells compared to the levels in CD40L^- T_FC cells in the analysis of healthy individuals. T_FC and its subsets were analyzed in CLL patients and healthy individuals, T_FC and CD40L⁺ T_FC cells were increased in CLL patients and there was a positive correlation between T_FC and CD5⁺CD19⁺ cells. Moreover, increased number of T_FC cells were detected in CLL patients with more progressive disease. Higher expression level of IL-4, IL-17, IL-21, and IFN-γ was observed in CD40L⁺ T_FC cells of patients compared to the levels in healthy controls. Our findings might indicate that CD40L⁺ T_FC cells may have a B cell activating role rather than exhibiting a cytotoxic role. Considering the effects of CD40L⁺ T_FC cells on B cells, determining subsets of T_FC cells which differentiate and understanding the functions of these subsets is crucial to elucidate their roles in the pathogenesis of B cell malignancies.