When death starts with a caspase hen a cytotoxic lymphocyte delivers granzyme B to a target cell, current models emphasize that the enzyme induces apoptosis through a mitochondria-centered pathway, cleaving the proapoptotic Bcl-2 family member Bid to cause mitochondrial permeabilization. On page 875, Metkar et al. overturn this view, showing that in the dominant pathway granzyme B begins by pro...

It is well established that granzymes A and B play a role in CTL killing of target cells by the perforin-dependent granule exocytosis pathway. The functions of multiple additional granzymes expressed in CTL are less well defined. In the present studies, CTL generated from mice deficient in dipeptidyl peptidase 1 (DPP1) were used to investigate the contribution of granzyme C to CTL killing of al...

OBJECTIVE Systemic juvenile idiopathic arthritis (JIA) is associated with high levels of interleukin-6 (IL-6) in the serum and synovial fluid, and impairment of natural killer (NK) cell function is often observed. This study was undertaken to evaluate a possible link between these 2 biologic findings and whether they may be associated with the development of macrophage activation syndrome, a co...

Granzymes are a family of granule-associated serine esterases that mediate apoptosis by cytotoxic T lymphocytes and natural killer cells. We have previously shown that cdc2, the mitosis-regulating cyclin-dependent kinase, is required for granzyme B-induced apoptosis in target cells. In addition, granzyme B induces premature activation and tyrosine dephosphorylation of cdc2 during apoptosis. Thr...

Caspases and granzyme B are proteases that share the primary specificity to cleave at the carboxyl terminal of aspartate residues in their substrates. Both, caspases and granzyme B are enzymes that are involved in fundamental cellular processes and play a central role in apoptotic cell death. Although various targets are described, many substrates still await identification and many cleavage si...

When death starts with a caspase hen a cytotoxic lymphocyte delivers granzyme B to a target cell, current models emphasize that the enzyme induces apoptosis through a mitochondria-centered pathway, cleaving the proapoptotic Bcl-2 family member Bid to cause mitochondrial permeabilization. On page 875, Metkar et al. overturn this view, showing that in the dominant pathway granzyme B begins by pro...

Serine protease granzyme B plays important roles in infections, autoimmunity, transplant rejection, and antitumor immunity. A triple-mutated granzyme B variant that encodes three amino substitutions (Q48R, P88A, and Y245H) has been reported to have altered biological functions. In the polymorphism rs8192917 (2364A>G), the A and G alleles represent wild type QPY and RAH mutant variants, respecti...

Background: Studies on efficacy of various vaccines that prevent or reduce the primary and recurrent HSV-1 infection have demonstrated the importance of cellular immunity for protection against the infection. We previously used DNA vaccination to induce cellular immunity against HSV-1 infection in mice. Objective: The aim of our study was to evaluate the effect of LIGHT, a member of TNF super f...

Acute myeloid leukemia (AML) cells of subtypes M4 and M5 show enhanced expression of CD64 (FcgammaRI), the high-affinity receptor for IgG, which is normally expressed at high levels only on activated cells of the myeloid lineage. CD64 is therefore a prime target for the specific delivery of cytotoxic agents. A promising toxin candidate is granzyme B, a human serine protease originating from cyt...