Expression and production of interleukin 4 in B-cell chronic lymphocytic leukaemia.
Interleukin (IL) 4 is a T-cell derived pleiotropic cytokine whose properties include alterations of B-cell function. In B-cell chronic lymphocytic leukaemia (B-CLL), IL4 is involved in the mechanism of survival of the leukaemic B-cells. The present study examines the expression and production of IL4 by B- and T-lymphocytes derived from patients with B-CLL and provides evidence that IL4 is not an autocrine factor in B-CLL. Freshly isolated B-CLL cells enriched for B- and T-cells did not express mRNA for IL4 but expressed mRNA for IL4 receptor (IL4R). Activation of B-cells with phorbol ester and calcium ionophore and of T-cells with phytohaemaglutinin (PHA) upregulated IL4 mRNA expression. However phorbol ester and calcium ionophore did not affect the mean level of IL4 production by either B-CLL or normal B-cells. Furthermore, in the presence or absence of activation, the amount of IL4 synthesised by B-CLL B-cells was not significantly different than that observed with peripheral blood B-cells isolated from normal individuals (with activation: P=0.239; without activation: P=0.565). Also, there was no significant difference between normal and B-CLL B-cells in the level of cytoplasmic IL4 (P=0.47). PHA-activated enriched B-CLL T-cells produced significantly higher levels of IL4 compared to normal control T-cells (P=0.0136). In addition, in 47% of cases with B-CLL T-cells, a significant higher level of intracellular IL4 was observed (P=0.0027). The levels of production of IL4 by the T-cell-enriched preparations correlated positively with the intensity of cytoplasmic L4 in CD4+ and CD8+ cells in tested samples (r=0.49 and r=0.76, respectively). The significant differences observed in the production of IL4 by B-CLL B- and T-lymphocytes may suggest a paracrine function of IL4 in B-CLL.
Mainou-Fowler
T
T
University Department of Haematology, School of Clinical and Laboratory Sciences, Royal Victoria Infirmary, Newcastle-upon-Tyne, UK. Tryfonia.Mainou-Fowler@ncl.ac.uk
Proctor
S J
SJ
Miller
S
S
Dickinson
A M
AM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D003593:Cytoplasm / Q000737:chemistry; D005434:Flow Cytometry; D006801:Humans; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000235:genetics; D015448:Leukemia, B-Cell / Q000209:etiology / Q000378:metabolism*; D008875:Middle Aged; D019899:Paracrine Communication; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism
D012333:RNA, Messenger; D015847:Interleukin-4