Both CD4+ FoxP3+ and CD4+ FoxP3− T cells from patients with B-cell malignancy express cytolytic markers and kill autologous leukaemic B cells in vitro

摘要

Cytotoxic CD4⁺ T cells have been found in patients with chronic lymphocytic leukaemia (CLL) and seem to be involved in the regulation of malignant B cells. The CD4⁺ T regulatory cells (Tregs) can regulate various immune cells, including B cells, by inducing their apoptosis. Hence, different subgroups of CD4⁺ T cells may be involved in the regulation of malignant B cells. In this study, the cytotoxic phenotype and function of various CD4⁺ T-cell subgroups were investigated in patients with B-cell malignancies. Peripheral blood was collected from patients with CLL, various B-cell lymphomas, healthy adult donors, children with precursor B-cell acute lymphoblastic leukaemia (pre-B ALL) and from healthy children. CD4⁺ T cells (CD3⁺ CD4⁺ FoxP3⁻), Tregs (CD3⁺ CD4⁺ CD127^low FoxP3⁺) and CD127^high FoxP3⁺ T cells (CD3⁺ CD4⁺ CD127^high FoxP3⁺) were analysed for their expression of the cytolytic markers CD107a and Fas ligand. Patients with CLL had increased CD107a expression on all tested T-cell subgroups compared with healthy donors. Similar results were found in patients with B-cell lymphomas whereas the CD107a expression in children with pre-B ALL was no different from that in healthy controls. Fas ligand expression was similar between patient cells and cells of healthy donors. CD4⁺ T cells and Tregs from patients with CLL and healthy donors were subsequently purified and cultured in vitro with autologous B cells. Both subgroups lysed B cells and killing was confirmed by granzyme ELISAs. In conclusion, cytotoxic populations of CD4⁺ T cells, including Tregs, are present in patients with B-cell malignancy and may be an important factor in immune-related disease control.