Thymosin alpha 1 modulates the expression of high affinity interleukin-2 receptors on normal human lymphocytes (original) (raw)

1990, International Journal of Immunopharmacology

In this report we demonstrate that thymosin alpha 1 (Tat), 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 Ta~. In most experiments the high and low concentration peaks of activity were observed at 10 8 M and 10-~2M, respectively, although peak responses were observed at different Ta~ 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. It is widely accepted that biologic responsiveness to interleukin-2 (IL-2) is mediated by the high affinity IL-2 receptor (IL-2R), a heterodimer consisting of an a chain associated with a/3 chain. The IL-2R a chain binds IL-2 with low affinity and is recognized by the anti-Tac monoclonal antibody (mAb), while the /3 chain binds IL-2 with intermediate affinity (Robb, Greene & Rusk, 1984; Robb & Rusk, 1986; Tsudo, Kozak, Goldman & Waldmann, 1986). Although the biological role of intermediate affinity IL-2R is still undefined, it has been reported that intermediate affinity IL-2R (p70/75; /3-chain) mediate internalization of bound ligand and it is likely to be involved in intracellular signal transduction pathways (