Relationship between cytokine receptors and lymphocyte activation.

Abstract

In the immunological field, many substances that have biological activities on lymphocytes or hematopoietic cells have been purified and cloned. These substances are called “lymphokines” or “cytokines”, and have important roles on cell activation and differentiation. Cytokines have been proved to affect the wide variety of target cell through their receptors in “autocrine” or “paracrine” manner. They are also produced by the many kind of cells other than lymphocytes or hematopoietic cells, and sometimes have multifunctions in the same molecules.ADF (ATL-derived factor), which we have purified and cloned as an IL2R/p55 (Tac) inducing factor from the HTLV-I infected T-cell line, has high homologus DNA sequence to E. coli thioredoxin. As is the case with the E. coli thioredoxin, ADF has active disulfide bond and potent reducing activity and radical scavenging activity. ADF is also homologous to PDI (Protein Disulfide Isomerase) and has similar isomerase activity. Whereas ADF doesn't have the signal peptide, ADF is released to culture supernatant and has synergistic or additive effects with cytokines including IL-1 and IL-2 on the mitogenic response of some lymphoid cell lines. ADF is highly expressed in many virus-transformed cell lines such as HTLV-I, EBV, HPV and induced in the PHA-stimulated blast of normal PBL. These finding suggest the multifunctional property of ADF/Thioredoxin and the association with the cell activation or blastic transformation.Majority of EBV-transformed B cell lines express the low affinity Fc receptor for IgE (FceRII) which is an animal lectin-like protein and is identical to an activation antigen on B cells (CD23). FceRII/CD23 is expressed on the wide variety of hematopoietic cell lines including EBV (+) B and some HTLV-I (+) T cell lines. These cell lines released the soluble form of FceRII to the culture supernatant by proteolysis. Soluble FceRII has been called as IgE binding factor, which has affinity to IgE and other biological activities including growth promoting activity on lymphocytes. Membrane associated FceRII/CD23 has been proved to be associated with some tyrosine kinase, indicating that IgE or some other ligand may induce activation signal through the FceRII/CD23.The possible role of ADF in the induction of IL-2R/p55 (Tac) as well as FceRII/CD23 is discussed in relation to the normal and abnormal trasformation of lymphocytes.