IL-2 receptor and Fc epsilon R2 gene activation in lymphocyte transformation: possible roles of ATL-derived factor

Lymphocyte transformation/activation is accompanied by the induction of a variety of the inducible receptors associated with the activation antigens. The p55 chain of the interleukin-2 receptor (IL-2R/p55) recognized by anti-Tac monoclonal antibody (mAb) is expressed on activated T and B cells as well as natural killer (NK) cells. IL-2R/p55(Tac) is constitutively expressed on T4(+) T cells transformed by human T-lymphotropic virus I (HTLV-I), which is a causative agent for adult T-cell leukemia (ATL). Low affinity Fc receptor for IgE (Fc epsilon R2/CD23) is another inducible receptor binding IgE and is expressed on various hematopoietic cell types. While the physiological expression of Fc epsilon R2 and its soluble form (IgE Binding Factor; IgE BF) is variably regulated by cytokines and IgE, there is a constitutive expression of Fc epsilon R2 on Epstein-Barr virus (EBV) transformed B cell lines and some of HTLV-I (+) T cell lines. ATL-derived factor (ADF) has been characterized as an IL-2R/p55(Tac) inducing factor derived from HTLV-I(+) T cell lines. Purification of ADF protein and the cDNA cloning proved that ADF is closely related to the autocrine growth factor produced by an EBV(+) B cell line 3B6 (H. Wakasugi and T. Tursz) and belonging to the family of thiol reducing co-enzyme thioredoxin which is involved in many biological reactions. Recombinant ADF produced by COS cells and E. coli showed both IL-2R inducing and reducing activities. We will discuss the biological roles of ADF in viral and normal lymphocyte activation and transformation in relation to the receptor gene activation.