Affordable Access

In Vitro– and Ex Vivo–derived Cytolytic Leukocytes from Granzyme A × B Double Knockout Mice Are Defective in Granule-mediated Apoptosis but not Lysis of Target Cells

Journal of Experimental Medicine
The Rockefeller University Press
Publication Date
  • Brief Definitive Report
  • Brief Definitive Reports


Granzyme (gzm) A and gzmB have been implicated in Fas-independent nucleolytic and cytolytic processes exerted by cytotoxic T (Tc) cells, but the underlying mechanism(s) remains unclear. In this study, we compare the potential of Tc and natural killer (NK) cells of mice deficient in both gzmA and B (gzmA×B−/−) with those from single knockout mice deficient in gzmA (−/−), gzmB (−/−), or perforin (−/−) to induce nuclear damage and lysis in target cells. With the exception of perforin−/−, all in vitro– and ex vivo–derived Tc and NK cell populations from the mutant strains induced 51Cr-release in target cells at levels and with kinetics similar to those of normal mice. This contrasts with their capacity to induce apoptotic nuclear damage in target cells. In gzmA×B−/− mice, Tc/NK-mediated target cell DNA fragmentation was not observed, even after extended incubation periods (10 h), but was normal in gzmA-deficient and only impaired in gzmB-deficient mice in short-term (2–4 h), but not long-term (4–10 h), nucleolytic assays. This suggests that gzmA and B are critical for Tc/NK granule– mediated nucleolysis, with gzmB being the main contributor, while target cell lysis is due solely to perforin and independent of both proteases.

There are no comments yet on this publication. Be the first to share your thoughts.