Interactions Between Zinc and Thymulin

Thymulin (formerly called "Facteur Thymique Sérique or FTS) is a metallopeptidic hormone selectively produced by thymic epithelial cells (TEC) and known to induce intra and extra-thymic T cell differentiation. It was initially isolated from porcine serum and shown to be present in calf thymus extract. Its amino-acid sequence was determined (<Glu-Ala-Lys-Ser-Gln-Gly-Gly-Ser-Asn). It is a nonapeptide whose biological activity is dependent on the presence of zinc, in an equimolecular ratio. The metallopeptide thus formed bears a specific tridimensional conformation detected by nuclear magnetic resonance studies, and that yielded a new monoclonal antibody-defined epitope. The presence of zinc and metallothionein has been demonstrated within TEC which produce the peptide, suggesting that the molecule is secreted in its active zinc-containing form. The zinc/thymulin relationship, was further studied using various models of mild zinc deficiency in experimental animals and in humans. Serum thymulin activity was decreased as a result of zinc deficiency, and was corrected by in vivo and in vitro zinc supplementation, suggesting that this parameter could be a sensitive indicator of zinc deficiency. When considered together with the parallel variations seen in T-cell subpopulations and lymphokine production, these observations could provide a possible explanation of the role of zinc on T cell functions.