Truncated thioredoxin is a mitogenic cytokine for resting human peripheralblood mononuclear cells and is present in human plasma

Human thioredoxin (Trx) catalyzes intracellular disulfide reductions but ha s also co-cytokine activity with interleukins after leaderless secretion. A recombinant truncated form of thioredoxin with the 80 N-terminal residues (Trx80) was purified to homogeneity, We discovered that Trx80 by itself is a potent mitogenic cytokine stimulating growth of resting human peripheral blood mononuclear cells. No effect was seen by Trx, but Trx80 at 50-100 nm induced cell proliferation of human peripheral blood mononuclear cells in s erum-free synthetic medium, measured as [H-3]thymidine incorporation after 72 h, with a maximum effect being comparable with that of 5 units/ml of int erleukin-a. Trx80 lacked redox activity, but CD spectra suggested a seconda ry structure similar to Trx. Reduced Trx80 had an M-r of 25,000, indicating that it is a dimer in solution. We also developed two different sandwich e nzyme-linked immunosorbent assays that distinguish between full-length Trx and Trx80 and determined plasma levels of Trx and Trx80 in blood donors. Th e levels of Trx80 varied from 2 to 175 ng/ml; in comparison levels of Trx v aried from 16 to 55 ng/ml without correlation to Trx80, In conclusion, the naturally occurring Trx80 is a novel mitogenic cytokine for normal resting human blood mononuclear cells.