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.