Immunomodulatory Effect and Acetylcholine Receptor Binding of a Thymopeptide (Tp4) on Human Peripheral Blood Lymphocytes

Abstract

The effect of a synthetic thymopeptide, Tp4 (RGH 0206) on nAChR binding capacity and stimulatory responses of normal human peripheral lymphocytes were studied. The present study is the first to demostrate that Tp4 binds to the nAChR on PBLs and this binding is resulted in rapid modulatory effect on the activation signal and affects also the proliferative response. The inhibitory effect of Tp4 on 125Iα-Btx or 3H-nicotine binding was in correlation with a rapid increase of cGMP-level. Another activation parameter; AChE activity, showing the same concentration dependency, was declined reaching the maximal effect in the same, 6–60 nM, range. After a 72h incubation with suboptimal dose of PHA, both proliferation rate and AChE activity were inhibited. The results are in good agreement with earlier observations on the suppressive nature of nAChR on PBLs and on binding of thymopeptides to nAChR from electric tissue, as well as with the reported inhibiting effect of thymus hormones on IL-2 production. The present data might have relevance to the pathogenesis and diagnostics of myasthenia gravis, because the binding of overproduced thymopeptides to nAChRs in various organs could lead to different effects, i.e. to altered cholinergic transmission at the neuromuscular junctions and to the alteration of lymphocyte functions on PBLs and on thymocytes too.