Cellular Peptidases in Immune Functions and Diseases

S Ansorge, F Bühling, T Kähne, U Lendeckel, D Reinhold, M Täger, S Wrenger, Ansorge, Siegfried, Bühling, Frank, Kähne, Thilo, Lendeckel, Uwe, Reinhold, Dirk, Täger, Michael, Wrenger, Sabine, Siegfried Ansorge, Frank Bühling, Thilo Kähne, Uwe Lendeckel, Dirk Reinhold, Michael Täger, Sabine Wrenger

DP IV/CD26 is involved in regulation of DNA synthesis and proliferation as well as production of cytokines of hematopoietic cells under various conditions. Inhibition of DNA synthesis in T lymphocytes, B lymphocytes, NK cells and myelomonocytic cells as well as of the production of IL-2, IL-6 TNF alpha, IL-1, IL-10, IL-12, IL-13, IFN-gamma, GM-CSF are not due to apoptosis of these cells. DP IV/CD26 inhibitors induce TGF-beta 1 mRNA synthesis and latent protein release demonstrating a crucial role of TGF-beta 1 in mediating CD26 function. X-X-Pro peptides as HIV-Tat protein strongly inhibit DP IV enzymatic activity and suppress DNA synthesis. This group of peptides may represent a class of natural DP IV/CD26 ligands and effectors, respectively. Hyperphosphorylation of p56lck as well as protein tyrosine phosphorylation of a number of proteins in T lymphocytes can be modulated by DP IV inhibitors. These data suggest that enzymatic activity or, at least in part, the active site of DP IV are both essential for its regulatory function in lymphocytes. Further work is required to determine the natural ligands, i.e. substrates and effectors, which are play the central role in DP IV/CD26 action in T cell growth and to understand the molecular mechanism of the early steps of this fundamental process.