ATL-derived factor (ADF), an IL-2 receptor/Tac inducer homologous to thioredoxin; possible involvement of dithiol-reduction in the IL-2 receptor induction.
HTLV-I transformed T cells not only express a large number of interleukin-2 receptors [IL-2R/p55(Tac)], but also produce a factor named ATL-derived factor (ADF) that augments the expression of IL-2R/p55(Tac). Based on a partial N-terminal amino acid sequence, complementary DNA (cDNA) clones for human and mouse ADF were isolated and sequenced. Recombinant ADF produced by COS-7 monkey kidney cells showed IL-2R/Tac inducing activity on YT cells, which are sensitive for ADF. ADF mRNA was strongly expressed in HTLV-I(+) T cells lines, but not in inactivated cells (THP-1, unstimulated PBMC). Furthermore, in normal human peripheral blood mononuclear cells, the expression of ADF mRNA was enhanced by mitogens or phorbol myristate acetate, suggesting a possible involvement of ADF in the lymphocyte activation. Homology analysis revealed an unexpected relationship between ADF and dithiol-reducing enzyme, thioredoxin, involved in many important biological reactions such as the conversion of ribonucleotides into deoxyribonucleotides, or the stabilization of glucocorticoid receptors. The biological significance of the generation of a redox potential in lymphocyte activation, and the possible involvement of dithiol reduction in the induction of IL-2R/Tac are discussed.
Tagaya
Y
Y
Institute for Immunology, Faculty of Medicine, Kyoto University, Japan.
Maeda
Y
Y
Mitsui
A
A
Kondo
N
N
Matsui
H
H
Hamuro
J
J
Brown
N
N
Arai
K
K
Yokota
T
T
Wakasugi
H
H
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002472:Cell Transformation, Viral; D003001:Cloning, Molecular; D016207:Cytokines; D004247:DNA / Q000235:genetics; D004220:Disulfides / Q000378:metabolism; D015368:Human T-lymphotropic virus 1; D006801:Humans; D008213:Lymphocyte Activation; D051379:Mice; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D010084:Oxidation-Reduction; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D013879:Thioredoxins / Q000378:metabolism
D016207:Cytokines; D004220:Disulfides; D009363:Neoplasm Proteins; D015375:Receptors, Interleukin-2; C055533:adult T cell leukemia-derived factor; D013879:Thioredoxins; D004247:DNA