Effect of Escherichia-coli thioredoxin, a homolog to the adult T-cell leukemia-derived factor, on epstein-barr virus-transformed B-lymphocytes

Abstract

In order to investigate the role of autocrine growth factors on cell growth of Epstein-Barr virus (EBV)-transformed human B lymphocytes, we have studied the effect of E. coli recombinant thioredoxin (r-thioredoxin), a homologue of adult-T-cell leukemia-derived factor (ADF), on the cell growth of various human lymphoid cell lines, either EBV-positive or -negative. It was found that, in serum-free culture conditions, exogenous r-thioredoxin increases DNA synthesis in lymphoblastoid and Burkitt's cell lines, independently of EBV genome expression; moreover, the combined effect of r-thioredoxin and interleukin-I (IL-1) or IL-6 resulted in a marked increase in DNA synthesis in lymphoblastoid cells, but not in Burkitt's cell lines. Anti r-thioredoxin monoclonal antibodies were developed and used to test the possibility of interfering with r-thioredoxin-induced cell proliferation. It was found that the growth-promoting activity of r-thioredoxin was inhibited by an anti-r-thioredoxin monoclonal antibody in a dose-dependent manner in P3HR-1 cells, a Burkitt's lymphoma cell line harboring an EBNA-2-defective virus, but not in other lymphoid cell lines, thus indicating that target cells may play an active role in antibody-mediated thioredoxin neutralization.