TY - JOUR
T1 - Cytotoxic lymphocytes require granzyme B for the rapid induction of DNA fragmentation and apoptosis in allogeneic target cells
AU - Heusel, Jonathan W.
AU - Wesselschmidt, Robin L.
AU - Shresta, Sujan
AU - Russell, John H.
AU - Ley, Timothy J.
N1 - Funding Information:
We thank the Steve Potter lab for D3 ES cells and their generous expertise, Pam Goda for animal husbandry, Brian Rush and Kathleen Maloney for excellent technical assistance, Ruduan Wang for her help with thymocyte assays, Bob Henry for electron microscopy, and Charlie Roberts, Phil Horn&z, Jay Grisolano, Dan Link, and especially Steve Lee for helpful advice. Diana Coleman-Peters provided expert assistance in preparation of this manuscript. A final thanks to Jean Heusel for her continuing support. Support for this work was provided by the National Institutes of Health (grant CA-49712) the Washington University-Monsanto Agreement, and a grant from the Mallinckrodt Foundation (T. J. L.).
PY - 1994/3/25
Y1 - 1994/3/25
N2 - We have generated H-2b mice with a homozygous null mutation in the granzyme (gzm) B gene. Gzm B is a neutral serine protease with Aspase activity that is found only in the granules of activated cytolytic T cells, natural killer cells, and lymphokine-activated killer cells. Gzm B-/- mice develop normally and have normal hematopoiesis and lymphopoiesis. In vitro, cytotoxic T lymphocytes (CTL) derived from gzm B-/- animals are able to induce 51Cr release from allotarget cells, but with reduced efficiency. However, gzm B-/- CTL have a profound defect in their ability to induce rapid DNA fragmentation and apoptosis in allogeneic target cells. This defect is kinetic since DNA fragmentation is partially compensated and 51Cr release is completely resuced with long incubation times. We conclude that gzm B serves a critical and nonredundant role for the rapid induction of target cell DNA fragmentation and apoptosis by alloreactive cytotoxic T lymphocytes.
AB - We have generated H-2b mice with a homozygous null mutation in the granzyme (gzm) B gene. Gzm B is a neutral serine protease with Aspase activity that is found only in the granules of activated cytolytic T cells, natural killer cells, and lymphokine-activated killer cells. Gzm B-/- mice develop normally and have normal hematopoiesis and lymphopoiesis. In vitro, cytotoxic T lymphocytes (CTL) derived from gzm B-/- animals are able to induce 51Cr release from allotarget cells, but with reduced efficiency. However, gzm B-/- CTL have a profound defect in their ability to induce rapid DNA fragmentation and apoptosis in allogeneic target cells. This defect is kinetic since DNA fragmentation is partially compensated and 51Cr release is completely resuced with long incubation times. We conclude that gzm B serves a critical and nonredundant role for the rapid induction of target cell DNA fragmentation and apoptosis by alloreactive cytotoxic T lymphocytes.
UR - http://www.scopus.com/inward/record.url?scp=0028258577&partnerID=8YFLogxK
U2 - 10.1016/0092-8674(94)90376-X
DO - 10.1016/0092-8674(94)90376-X
M3 - Article
C2 - 8137431
AN - SCOPUS:0028258577
SN - 0092-8674
VL - 76
SP - 977
EP - 987
JO - Cell
JF - Cell
IS - 6
ER -