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Dendritic cells in patients with non‐progressive B‐chronic lymphocytic leukaemia have a normal functional capability but abnormal cytokine pattern
Author(s) -
Rezvany Mohammad Reza,
JeddiTehrani Mahmood,
Biberfeld Peter,
Söderlund Johan,
Mellstedt Håkan,
Österborg Anders,
Rabbani Hodjattallah
Publication year - 2001
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.2001.03117.x
Subject(s) - cd80 , dendritic cell , interleukin 3 receptor , cd86 , immunology , cd11c , cd14 , biology , major histocompatibility complex , mhc class ii , interleukin 4 , cytokine , granulocyte macrophage colony stimulating factor , chronic lymphocytic leukemia , t cell , immune system , cd40 , flow cytometry , leukemia , phenotype , in vitro , gene , cytotoxic t cell , biochemistry
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‐12p 35 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.