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1
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0028219791
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Cytotoxicity mediated by T cells, natural killer cells is greatly impaired in perforin-deficient mice
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Kagi D., Ledermann B., Burki K., Seiler P., Odermatt B., Olsen K.J., Podack E.R., Zinkernagel R.M., Hengartner H. Cytotoxicity mediated by T cells, natural killer cells is greatly impaired in perforin-deficient mice. Nature. 369:1994;31-37.
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2
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0031899584
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Dual mechanisms of apoptosis induction by cytolytic lymphocytes
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Trapani J.A. Dual mechanisms of apoptosis induction by cytolytic lymphocytes. Int Rev Cytol. 182:1997;111-192.
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Trapani, J.A.1
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3
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0031975821
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The relative role of lymphocyte granule exocytosis versus death receptor-mediated cytotoxicity in viral pathophysiology
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Smyth M.J., Trapani J.A. The relative role of lymphocyte granule exocytosis versus death receptor-mediated cytotoxicity in viral pathophysiology. J Virol. 72:1998;1-9.
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Smyth, M.J.1
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4
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0029083438
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Granzyme A-deficient mice retain potent cell-mediated cytotoxicity
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Ebnet K., Hausmann M., Lehmann-Grube F., Mullbacher A., Kopf M., Lamers M., Simon M.M. Granzyme A-deficient mice retain potent cell-mediated cytotoxicity. EMBO J. 14:1995;4230-4239.
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Lamers, M.6
Simon, M.M.7
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5
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0028258577
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Cytotoxic lymphocytes require granzyme B for the rapid induction of DNA fragmentation, apoptosis in allogeneic target cells
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Heusel J.W., Wesselschmidt R.L., Shresta S., Russell J.H., Ley T.J. Cytotoxic lymphocytes require granzyme B for the rapid induction of DNA fragmentation, apoptosis in allogeneic target cells. Cell. 76:1994;977-987.
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Heusel, J.W.1
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6
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Granule-mediated cytolysis of target cells
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Podack E.R. Granule-mediated cytolysis of target cells. Curr Top Microbiol Immunol. 140:1989;1-9.
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Perforin-mediated myocardial damage in acute myocarditis
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Young L.H., Joag S.V., Zheng L.M., Lee C.P., Lee Y.S., Young J.D. Perforin-mediated myocardial damage in acute myocarditis. Lancet. 336:1990;1019-1021.
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Lee, Y.S.5
Young, J.D.6
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8
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0026532606
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A natural killer cell granule protein that induces DNA fragmentation and apoptosis
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Shi L., Kraut R.P., Aebersold R., Greenberg A.H. A natural killer cell granule protein that induces DNA fragmentation and apoptosis. J Exp Med. 175:1992;553-566.
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Shi, L.1
Kraut, R.P.2
Aebersold, R.3
Greenberg, A.H.4
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9
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0026474805
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Purification of three cytotoxic lymphocyte granule serine proteases that induce apoptosis through distinct substrate and target cell interactions
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Shi L., Kam C.M., Powers J.C., Aebersold R., Greenberg A.H. Purification of three cytotoxic lymphocyte granule serine proteases that induce apoptosis through distinct substrate and target cell interactions. J Exp Med. 176:1992;1521-1529.
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Shi, L.1
Kam, C.M.2
Powers, J.C.3
Aebersold, R.4
Greenberg, A.H.5
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10
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0030892138
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Granzyme B (GraB) autonomously crosses the cell membrane, perforin initiates apoptosis and GraB nuclear localization
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Shi L., Mai S., Israels S., Browne K., Trapani J.A., Greenberg A.H. Granzyme B (GraB) autonomously crosses the cell membrane, perforin initiates apoptosis and GraB nuclear localization. J Exp Med. 185:1997;855-866.
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J Exp Med
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Shi, L.1
Mai, S.2
Israels, S.3
Browne, K.4
Trapani, J.A.5
Greenberg, A.H.6
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11
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10544252275
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New paradigm for lymphocyte granule-mediated cytotoxicity. Target cells bind, internalize granzyme B, but an endosomolytic agent is necessary for cytosolic delivery and subsequent apoptosis
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Froelich C.J., Orth K., Turbov J., Seth P., Gottlieb R., Babior B., Shah G.M., Bleackley R.C., Dixit V.M., Hanna W. New paradigm for lymphocyte granule-mediated cytotoxicity. Target cells bind, internalize granzyme B, but an endosomolytic agent is necessary for cytosolic delivery and subsequent apoptosis. J Biol Chem. 271:1996;29073-29079.
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Froelich, C.J.1
Orth, K.2
Turbov, J.3
Seth, P.4
Gottlieb, R.5
Babior, B.6
Shah, G.M.7
Bleackley, R.C.8
Dixit, V.M.9
Hanna, W.10
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13
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0033499729
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Bacterial toxins facilitate intracellular delivery of granzyme B: Evidence that endosomal disruption is an important function of perforin, in addition to transmembrane pore-formation
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The first study providing quantitative and kinetic data challenging the notion that perforin functions through simple transmembrane pore formation. The role of perforin in facilitating apoptosis can be replicated by endosomolytic agents and, in the apparent absence of sizeable transmembrane lesions, even in the presence of 'high' perforin concentrations.
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Browne K.A., Blink E., Sutton V.R., Froelich C.J., Jans D.A., Trapani J.A. Bacterial toxins facilitate intracellular delivery of granzyme B: evidence that endosomal disruption is an important function of perforin, in addition to transmembrane pore-formation. Mol Cell Biol. 19:1999;8604-8615. The first study providing quantitative and kinetic data challenging the notion that perforin functions through simple transmembrane pore formation. The role of perforin in facilitating apoptosis can be replicated by endosomolytic agents and, in the apparent absence of sizeable transmembrane lesions, even in the presence of 'high' perforin concentrations.
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(1999)
Mol Cell Biol
, vol.19
, pp. 8604-8615
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Browne, K.A.1
Blink, E.2
Sutton, V.R.3
Froelich, C.J.4
Jans, D.A.5
Trapani, J.A.6
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14
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0032475823
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An antimicrobial activity of cytolytic T cells mediated by granulysin
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The first instance of perforin-dependent killing, of an intracellular microbial pathogen, that does not appear to utilize granzymes.
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Stenger S., Hanson D., Teitelbaum R., Dewan P., Niazi K., Froelich C.J., Ganz T., Thoma-Uszynski S., Melian A., Bogdan C.et al. An antimicrobial activity of cytolytic T cells mediated by granulysin. Science. 282:1998;121-125. The first instance of perforin-dependent killing, of an intracellular microbial pathogen, that does not appear to utilize granzymes.
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(1998)
Science
, vol.282
, pp. 121-125
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Stenger, S.1
Hanson, D.2
Teitelbaum, R.3
Dewan, P.4
Niazi, K.5
Froelich, C.J.6
Ganz, T.7
Thoma-Uszynski, S.8
Melian, A.9
Bogdan, C.10
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15
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0033136316
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Apoptosis induced by granzyme B-glycosaminoglycan complexes: Implications for granule-mediated apoptosis in vivo
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The first paper to point out that the co-delivery of proapoptotic agents to the target cell is probably achieved in the context of macromolecular complexes containing chondroitin sulfate proteoglycans.
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Galvin J.P., Spaeny-Dekking L.H., Wang B., Seth P., Hack C.E., Froelich C.J. Apoptosis induced by granzyme B-glycosaminoglycan complexes: implications for granule-mediated apoptosis in vivo. J Immunol. 162:1999;5345-5350. The first paper to point out that the co-delivery of proapoptotic agents to the target cell is probably achieved in the context of macromolecular complexes containing chondroitin sulfate proteoglycans.
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(1999)
J Immunol
, vol.162
, pp. 5345-5350
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Galvin, J.P.1
Spaeny-Dekking, L.H.2
Wang, B.3
Seth, P.4
Hack, C.E.5
Froelich, C.J.6
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16
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0033178379
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Cytotoxic lymphocyte granules: Evolution of vesicles essential for combating virus infections
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Trapani J.A., Sutton V.R., Smyth M.J. Cytotoxic lymphocyte granules: evolution of vesicles essential for combating virus infections. Immunol Today. 20:1999;351-356.
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(1999)
Immunol Today
, vol.20
, pp. 351-356
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Trapani, J.A.1
Sutton, V.R.2
Smyth, M.J.3
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17
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0030907965
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Target cell lysis by CTL granule exocytosis is independent of ICE/Ced-3 family proteases
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Sarin A., Williams M.S., Alexander-Miller M.A., Berzofsky J.A., Zacharchuk C.M., Henkart P.A. Target cell lysis by CTL granule exocytosis is independent of ICE/Ced-3 family proteases. Immunity. 6:1997;209-215.
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Immunity
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Sarin, A.1
Williams, M.S.2
Alexander-Miller, M.A.3
Berzofsky, J.A.4
Zacharchuk, C.M.5
Henkart, P.A.6
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18
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0032530361
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Caspase dependence of target cell damage induced by cytotoxic lymphocytes
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The first paper to point out that nuclear damage, particularly DNA release, inflicted by cytotoxic lymphocytes requires caspase activation whereas non-nuclear parameters of cell death are largely independent of caspases.
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Sarin A., Haddad E.K., Henkart P.A. Caspase dependence of target cell damage induced by cytotoxic lymphocytes. J Immunol. 161:1998;2810-2816. The first paper to point out that nuclear damage, particularly DNA release, inflicted by cytotoxic lymphocytes requires caspase activation whereas non-nuclear parameters of cell death are largely independent of caspases.
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(1998)
J Immunol
, vol.161
, pp. 2810-2816
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Sarin, A.1
Haddad, E.K.2
Henkart, P.A.3
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19
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0032561352
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Efficient nuclear targeting of granzyme B, the nuclear consequences of apoptosis induced by granzyme B and perforin are caspase-dependent, but cell death is caspase-independent
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This paper first localised the essential proapoptotic effect of granzyme B as residing outside the nucleus. Cell death in response to granzyme B and perforin occurs irrespective of the apparent inhibition of nuclear damage by caspase inhibitors.
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Trapani J.A., Jans D.A., Browne K.A., Smyth M.J., Jans P.J., Sutton V.R. Efficient nuclear targeting of granzyme B, the nuclear consequences of apoptosis induced by granzyme B and perforin are caspase-dependent, but cell death is caspase-independent. J Biol Chem. 273:1998;27934-27938. This paper first localised the essential proapoptotic effect of granzyme B as residing outside the nucleus. Cell death in response to granzyme B and perforin occurs irrespective of the apparent inhibition of nuclear damage by caspase inhibitors.
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(1998)
J Biol Chem
, vol.273
, pp. 27934-27938
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Trapani, J.A.1
Jans, D.A.2
Browne, K.A.3
Smyth, M.J.4
Jans, P.J.5
Sutton, V.R.6
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20
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0032055097
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Granzyme B directly and efficiently cleaves several downstream caspase substrates: Implications for CTL-induced apoptosis
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This elegant and comprehensive paper shows that downstream caspase substrates can be targeted directly by granzyme B when caspases are inhibited.
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Andrade F., Roy S., Thornberry N., Rosen A., Casciola-Rosen L. Granzyme B directly and efficiently cleaves several downstream caspase substrates: implications for CTL-induced apoptosis. Immunity. 8:1998;451-460. This elegant and comprehensive paper shows that downstream caspase substrates can be targeted directly by granzyme B when caspases are inhibited.
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(1998)
Immunity
, vol.8
, pp. 451-460
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Andrade, F.1
Roy, S.2
Thornberry, N.3
Rosen, A.4
Casciola-Rosen, L.5
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21
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0033137079
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Granzyme A induces rapid cytolysis, a novel form of DNA damage independently of caspases
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Granzyme A loading into target cells was used to demonstrate for the first time that granzyme A can induce single-stranded DNA breaks in a caspase-independent manner. The significance of this finding is yet to be reported when using granzyme A deficient effector cells.
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Beresford P.J., Xia Z., Greenberg A.H., Lieberman J. Granzyme A induces rapid cytolysis, a novel form of DNA damage independently of caspases. Immunity. 10:1999;585-594. Granzyme A loading into target cells was used to demonstrate for the first time that granzyme A can induce single-stranded DNA breaks in a caspase-independent manner. The significance of this finding is yet to be reported when using granzyme A deficient effector cells.
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(1999)
Immunity
, vol.10
, pp. 585-594
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Beresford, P.J.1
Xia, Z.2
Greenberg, A.H.3
Lieberman, J.4
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22
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0028938366
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The target cell nucleus is not required for cell-mediated granzyme- Or Fas-based cytotoxicity
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Nakajima H., Golstein P., Henkart P.A. The target cell nucleus is not required for cell-mediated granzyme- or Fas-based cytotoxicity. J Exp Med. 181:1995;1905-1909.
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J Exp Med
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Nakajima, H.1
Golstein, P.2
Henkart, P.A.3
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23
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0033521626
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Mitochondria-dependent and -independent regulation of granzyme B-induced apoptosis
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MacDonald G., Shi L., Vande Velde C., Lieberman J., Greenberg A. Mitochondria-dependent and -independent regulation of granzyme B-induced apoptosis. J Exp Med. 189:1999;131-144.
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J Exp Med
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MacDonald, G.1
Shi, L.2
Vande Velde, C.3
Lieberman, J.4
Greenberg, A.5
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24
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0032752882
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Granzyme B-induced loss of mitochondrial inner membrane potential (Delta Psi m) and cytochrome c release are caspase independent
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This elegant study documented non-nuclear events that occur independently of caspases and that may influence cell survival.
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Helbein J.A., Barry M., Motyka B., Bleackley R.C. Granzyme B-induced loss of mitochondrial inner membrane potential (Delta Psi m) and cytochrome c release are caspase independent. J Immunol. 163:1999;4683-4693. This elegant study documented non-nuclear events that occur independently of caspases and that may influence cell survival.
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(1999)
J Immunol
, vol.163
, pp. 4683-4693
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Helbein, J.A.1
Barry, M.2
Motyka, B.3
Bleackley, R.C.4
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25
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0031570536
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Bcl-2 prevents apoptosis induced by perforin and granzyme B, but not that mediated by whole cytotoxic lymphocytes
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Sutton V.R., Vaux D.A., Trapani J.A. Bcl-2 prevents apoptosis induced by perforin and granzyme B, but not that mediated by whole cytotoxic lymphocytes. J Immunol. 158:1997;5783-5790.
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(1997)
J Immunol
, vol.158
, pp. 5783-5790
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Sutton, V.R.1
Vaux, D.A.2
Trapani, J.A.3
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26
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0033548065
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BCL-2 blocks perforin-induced nuclear translocation of granzymes, concomitant with protection against the nuclear events of apoptosis
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Jans D.J., Sutton V.R., Jans P.J., Froelich C.J., Trapani J.A. BCL-2 blocks perforin-induced nuclear translocation of granzymes, concomitant with protection against the nuclear events of apoptosis. J Biol Chem. 274:1999;3953-3961.
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J Biol Chem
, vol.274
, pp. 3953-3961
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Jans, D.J.1
Sutton, V.R.2
Jans, P.J.3
Froelich, C.J.4
Trapani, J.A.5
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27
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0042377711
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The human cytotoxic T cell granule protease granzyme H has chymotrypsin-like (chymase) activity, is taken up into cytoplasmic vesicles reminiscent of granzyme B-containing endosomes
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The first characterization of a chymase granzyme in human CTLs. This study utilized recombinant granzyme H expressed in insect Sf9 cells.
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Edwards K.M., Kam C-M., Powers J., Trapani J.A. The human cytotoxic T cell granule protease granzyme H has chymotrypsin-like (chymase) activity, is taken up into cytoplasmic vesicles reminiscent of granzyme B-containing endosomes. J Biol Chem. 274:1999;30468-30473. The first characterization of a chymase granzyme in human CTLs. This study utilized recombinant granzyme H expressed in insect Sf9 cells.
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(1999)
J Biol Chem
, vol.274
, pp. 30468-30473
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Edwards, K.M.1
Kam, C.-M.2
Powers, J.3
Trapani, J.A.4
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28
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0030014911
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Granzyme A is critical for recovery of mice from infection with the natural cytopathic viral pathogen, ectromelia
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Mullbacher A., Ebnet K., Blanden R.V., Hla R.T., Stehle T., Museteanu C., Simon M.M. Granzyme A is critical for recovery of mice from infection with the natural cytopathic viral pathogen, ectromelia. Proc Natl Acad Sci USA. 93:1996;5783-5787.
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(1996)
Proc Natl Acad Sci USA
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Mullbacher, A.1
Ebnet, K.2
Blanden, R.V.3
Hla, R.T.4
Stehle, T.5
Museteanu, C.6
Simon, M.M.7
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29
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0033598718
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Granzymes are essential downstream effector molecules for the control of primary virus infections by cytolytic leukocytes
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This is the first reported instance of a pathophysiological consequence of a granzyme deficiency. The investigators make the observation that CTLs equipped with normal levels of perforin but lacking granzymes A and B are specifically deficient in protecting the host from a natural mouse pathogen, the poxvirus ectromelia. Despite this, mice lacking granzymes A and B have no intrinsic problem with raising CTL responses. The defective response to ectromelia is virtually as profound as perforin-deficiency per se.
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Mullbacher A., Waring P., Tha Hla R., Tran T., Chin S., Stehle T., Museteanu C., Simon M.M. Granzymes are essential downstream effector molecules for the control of primary virus infections by cytolytic leukocytes. Proc Natl Acad Sci USA. 96:1999;13950-13955. This is the first reported instance of a pathophysiological consequence of a granzyme deficiency. The investigators make the observation that CTLs equipped with normal levels of perforin but lacking granzymes A and B are specifically deficient in protecting the host from a natural mouse pathogen, the poxvirus ectromelia. Despite this, mice lacking granzymes A and B have no intrinsic problem with raising CTL responses. The defective response to ectromelia is virtually as profound as perforin-deficiency per se.
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(1999)
Proc Natl Acad Sci USA
, vol.96
, pp. 13950-13955
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Mullbacher, A.1
Waring, P.2
Tha Hla, R.3
Tran, T.4
Chin, S.5
Stehle, T.6
Museteanu, C.7
Simon, M.M.8
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30
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0344097497
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Perforin is essential for control of ectromelia virus but not related poxviruses in mice
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Mullbacher A., Hla R.T., Museteanu C., Simon M.M. Perforin is essential for control of ectromelia virus but not related poxviruses in mice. J Virol. 73:1999;1665-1667.
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J Virol
, vol.73
, pp. 1665-1667
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Mullbacher, A.1
Hla, R.T.2
Museteanu, C.3
Simon, M.M.4
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31
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0345517173
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Poxvirus-encoded serpins do not prevent cytolytic T cell-mediated recovery from primary infections
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This elegant in vivo study reinforces the notion that CTLs recruited in the context of most antiviral responses can bypass antiapoptotic mechanisms erected by the pathogen.
-
Mullbacher A., Wallich R., Moyer R.W., Simon M.M. Poxvirus-encoded serpins do not prevent cytolytic T cell-mediated recovery from primary infections. J Immunol. 162:1999;7315-7321. This elegant in vivo study reinforces the notion that CTLs recruited in the context of most antiviral responses can bypass antiapoptotic mechanisms erected by the pathogen.
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(1999)
J Immunol
, vol.162
, pp. 7315-7321
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Mullbacher, A.1
Wallich, R.2
Moyer, R.W.3
Simon, M.M.4
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32
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0033136315
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Granzyme A initiates an alternative pathway for granule-mediated apoptosis
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+ CTLs mediating graft-versus-host disease inflict less potent tissue damage in the recipient if they are deficient in granzyme expression, especially granzyme A.
-
+ CTLs mediating graft-versus-host disease inflict less potent tissue damage in the recipient if they are deficient in granzyme expression, especially granzyme A.
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(1999)
Immunity
, vol.10
, pp. 595-605
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Shresta, S.1
Graubert, T.A.2
Thomas, D.A.3
Raptis, S.Z.4
Ley, T.J.5
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33
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0032895417
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The levels of soluble granzyme A and B are elevated in plasma and synovial fluid of patients with rheumatoid arthritis
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Tak P.P., Spaeny-Dekking L., Kraan M.C., Breedveld F.C., Froelich C.J., Hack C.E. The levels of soluble granzyme A and B are elevated in plasma and synovial fluid of patients with rheumatoid arthritis. Clin Exp Immunol. 116:1999;366-370.
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Clin Exp Immunol
, vol.116
, pp. 366-370
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Tak, P.P.1
Spaeny-Dekking, L.2
Kraan, M.C.3
Breedveld, F.C.4
Froelich, C.J.5
Hack, C.E.6
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34
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0029914132
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A cytosolic granzyme B inhibitor related to the viral apoptotic regulator cytokine response modifier A is present in cytotoxic lymphocytes
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Sun J., Bird C.H., Sutton V., McDonald L., Coughlin P.B., De Jong T.A., Trapani J.A., Bird P.I. A cytosolic granzyme B inhibitor related to the viral apoptotic regulator cytokine response modifier A is present in cytotoxic lymphocytes. J Biol Chem. 271:1996;27802-27809.
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(1996)
J Biol Chem
, vol.271
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-
Sun, J.1
Bird, C.H.2
Sutton, V.3
McDonald, L.4
Coughlin, P.B.5
De Jong, T.A.6
Trapani, J.A.7
Bird, P.I.8
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35
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0029582926
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The roles of perforin- And Fas-dependent cytotoxicity in protection against cytopathic and noncytopathic viruses
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Kagi D., Seiler P., Pavlovic J., Ledermann B., Burki K., Zinkernagel R.M., Hengartner H. The roles of perforin- and Fas-dependent cytotoxicity in protection against cytopathic and noncytopathic viruses. Eur J Immunol. 25:1995;3256-3262.
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Eur J Immunol
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Kagi, D.1
Seiler, P.2
Pavlovic, J.3
Ledermann, B.4
Burki, K.5
Zinkernagel, R.M.6
Hengartner, H.7
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36
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0033485408
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Compromised virus control and augmented perforin-mediated immunopathology in IFN-gamma-deficient mice infected with lymphocytic choriomeningitis virus
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Increased immunopathology mediated by perforin is observed when IFN-γ-deficient mice are infected with LCMV, indicating for the first time a role for both cytokine secretion and direct cytotoxicity in the control of this pathogen.
-
Nansen A., Jensen T., Christensen J.P., Andreasen S.O., Ropke C., Marker O., Thomsen A.R. Compromised virus control and augmented perforin-mediated immunopathology in IFN-gamma-deficient mice infected with lymphocytic choriomeningitis virus. J Immunol. 163:1999;6114-6122. Increased immunopathology mediated by perforin is observed when IFN-γ-deficient mice are infected with LCMV, indicating for the first time a role for both cytokine secretion and direct cytotoxicity in the control of this pathogen.
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(1999)
J Immunol
, vol.163
, pp. 6114-6122
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Nansen, A.1
Jensen, T.2
Christensen, J.P.3
Andreasen, S.O.4
Ropke, C.5
Marker, O.6
Thomsen, A.R.7
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37
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0033517288
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Rapid on/off cycling of cytokine production by virus-specific CD8+ T cells
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This elegant and comprehensive paper points out that the balance between direct cytotoxicity and release of inflammatory cytokines can be regulated at the single-cell level.
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Slifka M.K., Rodriguez F., Whitton J.L. Rapid on/off cycling of cytokine production by virus-specific CD8+ T cells. Nature. 401:1999;76-79. This elegant and comprehensive paper points out that the balance between direct cytotoxicity and release of inflammatory cytokines can be regulated at the single-cell level.
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