Abstract:
Recently, complementary DNA clones of human ADF were obtained from a cDNA library of the adult T-cell leukemia (ATL)-2 cells, using oligonucleotide probes based on the amino-acid sequence of human ATL-derived factor (ADF). ADF is highly homologous to the disulfide reducing enzyme thioredoxin found in prokaryotes and in mammalian cells. ADF expression was analyzed in both 3B6 (Epstein-Barr virus-containing B-cell line) and ATL-2 cells. Normal resting peripheral blood lymphocytes (PBL) did not express ADF mRNA, and a weak expression was seen in PBL stimulated with anti-CD3 monoclonal antibody alone. When PBL were stimulated maximally with anti-CD3 plus phorbol myristate acetate, the expression of ADF mRNA was increased markedly. Compared to ADF expression in maximally activated PBL, a strong signal was obtained in 3B6 cells and the pattern and intensities were similar to those of ATL-2 cells. The effects of Escherichia coli-produced recombinant (r) ADF on the proliferation of 3B6 cells also was examined. rADF promoted the growth of 3B6 cells at low cellular concentration (1 x 10(5)/ml) and in the absence of fetal calf serum (FCS). This effect was obtained dose-dependently between 0.1 and 10 ug/ml, whereas the effect was very low at high concentration or in the presence of FCS. ADF could act as a competence factor, allowing a cell to become sensitive to other growth factors. Preliminary results suggest that rADF is able to synergize not only with interleukin (IL)-1 and IL-2, but also with IL-4 and IL-6. ADF clearly appears to be involved in the upregulation of IL-2R on ATL and YT cells; it could exert a similar effect on other receptors of cytokines or growth factors. The recombinant thioredoxin of E coli, in the presence of thioredoxin-reductase and NADPH, can sustain 3B6 growth and synergize with IL-1 and IL-2, strongly suggesting that ADF exerts its effect on cellular proliferation through its reducing activity. (7 Refs)
Keywords: B-Lymphocytes/*IMMUNOLOGY Cell Line, Transformed Cell Transformation, Viral/GENETICS/*IMMUNOLOGY Cloning, Molecular Herpesvirus 4, Human/*GENETICS Human HTLV-I/*GENETICS Interleukin-1/*PHYSIOLOGY Interleukin-2/*PHYSIOLOGY Lymphocyte Transformation/IMMUNOLOGY Neoplasm Proteins/GENETICS/*PHYSIOLOGY RNA, Messenger/GENETICS Thioredoxin/*PHARMACOLOGY MONOGRAPH 920228
M9220890
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