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J. Exp. Med.,
Volume 186, Number 10, November 17, 1997 1781-1786
By

From the * Max-Planck-Institut für Immunbiology, Stübeweg 51, D-79108 Freiburg, Germany; 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
Institute of Biochemistry, University of Lausanne, CH-1066 Epalinges, Switzerland; and § Division
of Immunology and Cell Biology, John Curtin School of Medical Research, Australian National
University, Canberra City, A.C.T. 2601, Australia
/
) 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.
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