Binding of nuclear proteins to the negative regulatory element of the IL-2gene in lymphocytes from rheumatic patients

T lymphocytes from several autoimmune diseases including rheumatoid arthrit is (RA) and systemic lupus ergthematosus (SLE) exhibit deficient mitogenic response in terms of proliferation and IL-2 production. The expression of t he IL-2 gene is regulated by various transcription factors. One of these fa ctors suppresses IL-2 expression and binds to the negative responsive eleme nt in the IL-2 gene 5' flanking region (NRE-A), The authors hypothesized th at the decreased production of IL-2 by T cells from RA and SLE patients is at least partially caused hy high expression of the NRE-A binding protein. To test this hypothesis T cells from healthy donors and patients with RA an d SLE were stimulated. Using the electrophoretic mobility shift assay we de tected NRE-A DNA-binding proteins in the nuclei of the stimulated cells. No difference was found between NRE-A DNA binding in nuclear extracts of T ce lls taken from healthy donors and those taken from patients, The specificit y of the DNA-protein interactions was ascertained through the use of unlabe led DNA competitors. No correlation was found between DNA-binding and the p atients' disease duration or medication, In conclusion, decreased IL-2 bios ynthesis by T lymphocytes from RA and SLE patients can not be explained by abnormal expression of the NRE-A DNA-binding protein. (C) 1999 Academic Pre ss.