Cytotoxic T lymphocytes (CTLs) eliminate virus-infected tumor cells or alloantigen through a lyric mechanism, which involves the secretion of a cytoplasmic granules containing cytotoxic proteins, perforin and granzymes, of which the two most important are granzyme A and granzyme B. Perforin interacts with cell membranes and allows the access of granzymes into the target cell, inducing cell death by apoptosis.

A group of the Department of Biochemistry, University of Zaragoza, in collaboration with members of the Max-Planck Institute for Immunobiology in Freeburg, Germany, has used CTL integers from knockout mice for these cytotoxic proteins in order to study how to induce death cell. Thus, the use of lymphocytes from mice that had been deleted the expression of granzyme B (GzmB) or granzyme A (gzmA) has allowed them to study separately the mechanisms involving perforin and granzyme A, or perforin and granzyme B.

The authors conclude that the system perforin / granzyme B induces apoptosis through caspase activation, implicating the mitochondrial pathway, that the system perforin / granzyme A induces apoptosis through generation of free radicals, also by the mitochondrial pathway, but without activation of caspases, and granzymes A and B activate alternative cell death mechanisms that are independent of the pathways described so far. This study, which highlights the differences between the two granzymes mechanisms, is the first carried out under physiological conditions (CTL cytotoxi city assays with integers) on the subject.