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.