The T Cell Specific Serine Proteinase TSP-1: Biochemical Characterization, Genetic Analysis, and Functional Role
Activation of T lymphocytes by antigen leads to the production of a variety of hormone like factors - i.e. lymphokines (1) - and of effector molecules - i.e. leukolysins (2) - that either control cellular and humoral immune responses or exert effector functions. More recently a number of independent groups have identified several serine esterase(s) (3-5)/serine proteinase(s) (6,7) respectively, in T effector cells. In these and previous reports the involvement of proteolytic enzymes in T cell mediated processes such as cytolysis (3,8,9), induction of lymphocyte proliferation (7,10-12) and cellular migration (13,14) have been suggested. Here we describe the biochemical characterization and genetic analysis of a T cell specific serine proteinase with highly restricted substrate specificity, termed TSP-1, which was isolated from cloned murine cytolytic T lymphocytes. We demonstrate that TSP-1 is packaged into cytoplasmic granules of T effector cells and secreted into the extracellular space as a result of antigenic stimulation. Our functional studies indicate that TSP-1 is involved in the process of cell mediated lympholysis (CML) and in the T cell control of virus replication. Moreover the data suggest that the same enzyme regulates cellular proliferation and migration of lymphocytes.
KeywordsLeukemia Fractionation Serine Oncol Interferon
Unable to display preview. Download preview PDF.
- 2.H.S. Koren, Proposed classification of leukocyte-associated cytolytic molecules, Immunol. 8: 3 (1987).Google Scholar
- 6.M.D. Kramer, L. Binninger, V. Schirrmacher, H. Moll, M. Prester, G. Nerz, and M.M. Simon, Characterization and isolation of a trypsin-like serine protease from a long-term culture cytolytic T cell line and its expression by functionally distinct T cells, J. Immunol. 136: 4644 (1986).PubMedGoogle Scholar
- 14.M.M. Simon, H.G. Simon, U. Fruth, J. Epplen, H.K. Müller-Hermelink, and M.D. Kramer, Cloned cytolytic T-effector cells and their malignant variants produce an extracellular matrix degrading trypsin-like serine proteinase. Immunol. 60: 219 (1987).Google Scholar
- 16.U. Fruth, M. Prester, J.R. Golecki, H. Hengartner, H.G. Simon, M.D. Kramer, and M.M. Simon, The T cell specific serine proteinase TSP-1 is associated with cytoplasmic granules of cytolytic T lymphocytes, Eur. J. Immunol, in press (1987).Google Scholar
- 22.J.F. Brunet, M. Dosseto, F. Denizot, M.G. Mattei, W.R. Clark, T.M. Haqqi, P. Ferrier, M. Nabholz, A.M. Schmitt-Verhulst, M.F. Luciani, and P. Golstein, The inducible cytotoxic T-lymphocyte-associated gene transcript CTLA-1 sequence and gene localization to mouse chromosome 14, Nature 322 : 268 (1986).PubMedCrossRefGoogle Scholar
- 26.D. Masson, and J. Tschopp, Appearance of a lytic, pore-forming protein (perforin) from cytolytic T lymphocytes, J. Biol. Chem. 260: 9096 (1985).Google Scholar
- 27.M.M. Simon, U. Fruth, H.G. Simon, and M.D. Kramer, Evidence for the involvement of a T cell associated serine proteinase (TSP-1) in cell killing, 17th Forum in Immunol. Ann. Inst. Pasteur, 138: 285 (1987).Google Scholar
- 28.G.S.B. Ku, J.P. Quigley, and B.M. Sultzer, The inhibition of the mitogenic stimulation of B lymphocytes by a serine proteinase inhibitor: commitment to proliferation correlates with an enhanced expression of a cell-associated arginine-specific serine enzyme, J. Immunol. 131: 2494 (1983).PubMedGoogle Scholar