TY - JOUR
T1 - Granzyme a initiates an alternative pathway for granule-mediated apoptosis
AU - Shresta, Sujan
AU - Graubert, Timothy A.
AU - Thomas, Dori A.
AU - Raptis, Sofia Z.
AU - Ley, Timothy J.
N1 - Funding Information:
This work was supported by NIH grants DK49786 and CA49712 (T. J. L.). The authors would like to thank John Russell, Skip Virgin, and Christine Pham for critical advice and support throughout this project and Nancy Reidelberger for the preparation of the manuscript.
PY - 1999/5
Y1 - 1999/5
N2 - Granzyme (gzm) B-deficient cytotoxic lymphocytes (CTL) have a severe defect in the rapid induction of target cell apoptosis that is almost completely corrected by prolonged incubation of the CTL effectors and their targets. We show in this report that perforin-dependent, gzmB-independent cytotoxicity is caused by gzmA (or tightly linked genes). CTL deficient for gzmA and gzmB retain normal perforin function, but these CTL have a cytotoxic defect in vivo that is as severe as perforin-deficient CTL. Collectively, these results suggest that perforin provides target cell access and/or trafficking signals for the gzms, and that the gzms themselves deliver the lethal hits. The gzmA pathway appears to function independently from gzmB and may therefore provide a critical 'back-up' system when gzmB is inhibited in the target cell.
AB - Granzyme (gzm) B-deficient cytotoxic lymphocytes (CTL) have a severe defect in the rapid induction of target cell apoptosis that is almost completely corrected by prolonged incubation of the CTL effectors and their targets. We show in this report that perforin-dependent, gzmB-independent cytotoxicity is caused by gzmA (or tightly linked genes). CTL deficient for gzmA and gzmB retain normal perforin function, but these CTL have a cytotoxic defect in vivo that is as severe as perforin-deficient CTL. Collectively, these results suggest that perforin provides target cell access and/or trafficking signals for the gzms, and that the gzms themselves deliver the lethal hits. The gzmA pathway appears to function independently from gzmB and may therefore provide a critical 'back-up' system when gzmB is inhibited in the target cell.
UR - http://www.scopus.com/inward/record.url?scp=0033136315&partnerID=8YFLogxK
U2 - 10.1016/S1074-7613(00)80059-X
DO - 10.1016/S1074-7613(00)80059-X
M3 - Article
C2 - 10367905
AN - SCOPUS:0033136315
SN - 1074-7613
VL - 10
SP - 595
EP - 605
JO - Immunity
JF - Immunity
IS - 5
ER -