OBJECTIVE Proteolytic autoantigen cleavage by the serine protease granzyme B has been implicated in the development of systemic autoimmune disease; however, there has been no conclusive demonstration of a pathogenic role for granzyme B in autoimmunity. In this study, we evaluated the role of granzyme B in a murine model of autoimmunity. METHODS To identify potential novel granzyme B substrate...

Granzyme B is important for the ability of NK cells and CD8(+) T cells to kill their targets. However, we showed here that granzyme B-deficient mice clear both allogeneic and syngeneic tumor cell lines more efficiently than do wild-type (WT) mice. To determine whether regulatory T (Treg) cells utilize granzyme B to suppress immune responses against these tumors, we examined the expression and f...

Granzyme B is a unique serine protease, which plays a crucial role for target cell death. Several mechanisms of delivery of granzyme B to target cells have been recently identified. Granzyme B directly activates Bid, a specific substrate for granzyme B, resulting in caspase activation. Granzyme B efficiently cleaves many prominent autoantigens, and the hypothesis that autoantibodies arise when ...

Granzyme M is a serine protease known to be often expressed by natural killer cells and induce target cells apoptosis in combination with perforin. However, we detected granzyme M expression in murine and human cancer cell lines and human tumor samples in our study. Granzyme M increased chemoresistance, colony-formation, cytokine secretion and invasiveness in vitro. Most importantly, granzyme M...

Pancreatic beta cell destruction in type 1 diabetes is mediated by cytotoxic CD8(+) T lymphoctyes (CTL). Granzyme B is an effector molecule used by CTL to kill target cells. We previously showed that granzyme B-deficient allogeneic CTL inefficiently killed pancreatic islets in vitro. We generated granzyme B-deficient non-obese diabetic (NOD) mice to test whether granzyme B is an important effec...

Both the magnitude and function of vaccine-induced HIV-specific CD8+ CTLs are likely to be important in the outcome of infection. We hypothesized that rapid cytolysis by CTLs may facilitate control of viral challenge. Release kinetics of the cytolytic effector molecules granzyme B and perforin, as well as the expression of the degranulation marker CD107a and IFN-gamma were simultaneously studie...

Abstract Background and Aims Inflammatory Interstitial fibrosis tubular atrophy (i-IF/TA) is a prominent histological lesion reported in late biopsy poorly associated with graft survival. Cytotoxic T cell secrets Granzyme-B, which cleaves cytoskeleton protein, activates pro-IL-1β, TGF-β into their active form, leading to inflammation, fibrosis, the apoptosis target cell. The association of Gran...

OBJECTIVE T cell-induced cytotoxicity, of which granzyme B is a key mediator, is believed to contribute to the pathogenesis of inflammatory vascular diseases. In this report, we investigate the mechanism of granzyme B-induced smooth muscle cell (SMC) death. METHODS AND RESULTS The addition of purified granzyme B alone to cultured SMCs caused a significant reduction in cell viability. Chromati...

Granzyme B is a protease involved in the induction of rapid target cell death by cytotoxic lymphocytes. Definition of the substrate specificity of granzyme B allows for the identification of in vivo substrates in this process. By using the combinatorial methods of synthetic substrate libraries and substrate-phage display, an optimal substrate for granzyme B that spans over six subsites was dete...

Granzymes are a family of granule serine proteases found specifically in the cytotoxic granules of cytotoxic T lymphocytes and natural killer cells. Granzymes have features that are strongly conserved including: consensus sequences at their N-termini and around the three catalytic residues, activation from zymogemc forms, and conserved disuiphide bridges. However, there is good genetic evidence...