Role of ATL-derived factor (ADF) in the normal and abnormal cellular activation: involvement of dithiol related reduction.

HTLV-I transformed T cells not only express a large number of interleukin-2 receptors (IL-2R/p55(Tac], but also produce an IL-2R/Tac inducer named ATL-derived factor (ADF). We have cloned the ADF cDNA and found that ADF production in human lymphocytes can be enhanced by cellular activators such as mitogens or phorbol esters. Recombinant ADF produced by E. coli was shown to have growth-promoting activity in combination with interleukin-2 or suboptimal mitogenic stimuli on several lymphoid cells including human PBMCs, besides the originally reported IL-2R/Tac inducing activity. Homology analysis revealed an unexpected structural relationship between ADF and dithiol-reducing enzyme, thioredoxin, which had been characterized originally in prokaryotic system. Recombinant ADF also has a reducing activity, suggesting the presence of still unknown features of ADF action in vivo. The requirement of dithiol reduction in the biological activities of ADF, together with the possible involvement of ADF production in the normal and abnormal activation of human cells are discussed.