Effect of alpha-IFN on cytokine-induced antigen expression and secretion of TNF, LT and IgM in HCL.
In order to investigate the possible mechanisms for the effect of alpha-interferon (alpha-IFN) in hairy cell leukaemia (HCL), blood cells from 4 cases were treated in vitro with alpha-IFN, tumour necrosis factor (TNF) and interleukin 2 (IL-2). Changes in the antigen expression, immunoglobulin (Ig) secretion and the production of TNF and lymphotoxin (LT) were investigated. TNF induced expression of CD4 and CD71, increased the intensity of HLA-DR, CD25, CD11c and CD13 expression and decreased both the intensity and frequency of sIg and cIg positivity. alpha-IFN decreased CD25 expression, the tartrate-resistant acid phosphatase activity (TRAP), reduced the TNF-induced CD4 and CD71 expression and antagonized the TNF effect on the Ig expression. Spontaneous TNF or LT production could not be detected in culture supernatants. However, TNF was found to induce LT production, an effect which alpha-IFN antagonized and IL-2 augmented. The reduction of CD25, TNF-induced CD71 and TRAP caused by alpha-IFN seems to represent a deactivation of the activated state of hairy cells (HCs). The failure of alpha-IFN to induce Ig secretion or CD38 expression in HCs speaks against a differentiation induction effect. The LT secretion induced by TNF suggests that other cytokines than TNF might be involved in the proliferation of HCs and that alpha-IFN by blocking the production of LT and perhaps other cytokines causes a growth arrest in HCs.
Department of Pathology, University Hospital, Uppsala, Sweden.
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Hassan
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Lantz
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Sundström
D000328:Adult; D000368:Aged; D000943:Antigens, Differentiation / Q000378:metabolism*; D016207:Cytokines / Q000494:pharmacology*; D006801:Humans; D007075:Immunoglobulin M / Q000378:metabolism*; D016130:Immunophenotyping; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology; D007943:Leukemia, Hairy Cell / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008233:Lymphotoxin-alpha / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000494:pharmacology
D000943:Antigens, Differentiation; D016207:Cytokines; D007075:Immunoglobulin M; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007376:Interleukin-2; D008233:Lymphotoxin-alpha; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha