Dendritic cells in patients with non-progressive B-chronic lymphocytic leukaemia have a normal functional capability but abnormal cytokine pattern

Abstract

Dendritic cells (DC) are attractive candidates for use in vaccine-based immunotherapy. We have analysed the functional capability of DC generated in vitro from blood CD14+ cells of chronic lymphocytic leukaemia (CLL) patients and healthy donors by culturing for 10 d with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin 4 (IL-4) and tumour necrosis factor-α (TNF-α). Two distinct DC populations were identified in patients as well as in controls. The majority of DC expressed CD11c and a minority also CD123. Most of the DC generated from both patients and controls exhibited a mature phenotype indicated by CD83 and major histocompatibility complex (MHC) class II expression, as well as by a characteristic morphology. Less than 1% of DC exhibited CD14. CLL DC had a similar expression of accessory molecules (CD54, CD80 and CD86) as control DC. The mean fluorescence intensity of CD80 and MHC class I molecules was significantly higher on CLL DC than on control DC (P < 0.05). At the gene level (real-time polymerase chain reaction) the expression of IL-10 was higher in CLL (P = 0.028) than in control DC. IL-1β and IL-12p35 transcripts were also more abundant in CLL than in control DC but did not reach statistical significance. The expression of IL-4 and TNF-α was similar to that of control DC. The interferon γ (IFN-γ) gene expression level in CLL DC was decreased compared with control DC. DC of CLL patients had a similar capacity to stimulate in mixed leucocyte reaction as well as to present a recall antigen (PPD) as control DC. Thus, DC of CLL patients seem to have a normal function and may serve as antigen preserving cells for presentation of tumour antigens in a therapeutic vaccination approach. The mechanisms behind the observed increase in some surface molecules and the abnormal cytokine profile of CLL DC is not clear but might indicate pre-activation of DC in vivo, which may have a regulatory role in the pathobiology of CLL.