The role of CD40L-expressing CXCR5<SUP>+</SUP>CD8<SUP>+</SUP> 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-gamma, perforin, and granzyme-B levels were investigated in T-FC subsets. Increased levels of IL-4, IL-17, IL-21, IFN-gamma 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-gamma 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.