THYMOSIN ALPHA-1 MODULATES THE EXPRESSION OF HIGH-AFFINITY INTERLEUKIN-2 RECEPTORS ON NORMAL HUMAN-LYMPHOCYTES

In this report we demonstrate that thymosin alpha 1 (Tα1), a synthetic peptide composed of 28 amino acid residues, and thymosin fraction 5 (TF5) enhance the number of high affinity interleukin 2 receptors (IL-2R) expressed by human peripheral blood lymphocytes in response to in vitro stimulation with phytohemagglutinin (PHA). Thymosins did not, however, alter the affinity of the IL-2R for its ligand. Dose-response studies using a wide range of concentrations indicated a bimodal distribution of responsiveness to Tα1. In most experiments the high and low concentration peaks of activity were observed at 10-8M and 10-12M, respectively, although peak responses were observed at different Tα1 concentrations in different donors. No effects were elicited by thymosins in the absence of mitogenic stimulation. Thymosin enhancement of PHA-induced high affinity IL-2R expression directly correlated with increased levels of Tac antigen expression, as determined by flow cytometry, and enhanced interleukin 2 (IL-2) production. Since the biological effects of IL-2 are associated with the occupancy of high affinity IL-2R, the findings presented in this report strongly suggest that thymosins play a significant role in the regulation of immune responses through the modulation of high affinity IL-2R expression. © 1989.