Spectrum of extracellular matrix degrading enzymes in normal and malignantT lymphocytes

Human T cells produce and release fibronectin degrading neutral serine prot eases with a molecular weight of 50 kD, 70-80 kD (doublet) and 95 kD and ha ve a cell associated 400 kD fibronectin degrading enzyme. In addition, huma n T cells produce proteases with m.w. 50 70-80 kD and 400 kD which degrade laminin. CD 4+ T lymphocytes from a non-malignant cloned human T cell line produce a 92 kD gelatinase (MMP 9) and malignant T cell lines release, in a ddition to the 92 kD gelatinase, low amounts of a 72 kD gelatinase (MMP 2). Purification of the enzymatic activities using benzamidine sepharose yield s a 50 kD and a 70 kD band of which the 50 kD band has fibronectin degradin g capacity. The purified enzymes do not react with monoclonal antibodies to various previously characterized proteolytic enzymes present in T cells. T lymphocytes from a non-malignant cloned human T cell line produce high amo unts of the 50 and 70-80 kD proteases directly after stimulation with anti- CD 3 monoclonal antibodies wherafter the production of these enzymes declin es with time. The expression of the 400 kD fibronectin-degrading protease i s downregulated by crosslinking of alpha 4 beta 1-integrin receptors on T c ells using monoclonal antibodies. Thus, T lymphocytes produce several matri x degrading enzymes with multiple substrate specificities. The expression o f these enzymes is controlled partly by lymphocyte activation signals or by direct signalling via beta 1-integrins.