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.
KeywordsSerine Proteinase Effector Cell Percoll Gradient Cytoplasmic Granule Corneal Endothelial Cell
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