|
|
 Previous Article | Table of Contents | Next Article 
The role of granzyme B in murine models of acute graft-versus-host disease
and graft rejection
TA Graubert, JH Russell and TJ Ley
Department of Internal Medicine and Genetics, Washington University Medical
School, St Louis, MO 63110, USA.
A complete molecular description of the syndromes of graft-versus-host
disease (GVHD) and graft rejection could have a significant impact on
clinical bone marrow transplantation. Recent in vitro experiments (Heusel
et al, Cell 76:977, 1994 and Shresta et al, Proc Natl Acad Sci USA 92:5679,
1995) have shown that the putative mediators of these two syndromes,
cytotoxic lymphocytes (CTL) and natural killer (NK) cells, respectively,
initiate a program of cell death (apoptosis) in susceptible target tissues
in a manner critically dependent on the serine protease Granzyme B (gzm B).
In the present study, we have analyzed the phenotype of gzm B-deficient
mice using experimental transplant models designed to isolate their CD8+
CTL, CD4+ CTL, and NK compartments. We found a significant impairment in
class I-dependent GVHD mediated by gzm B -/- CD8+ CTL, whereas class
II-dependent GVHD was not altered using gzm B -/- CD4+ effectors. In a
hybrid resistance model, gzm B -/- hosts rejected haplo-identical marrow
grafts as efficiently as did their wild-type littermates. This result is
surprising in light of a severe defect in the ability of gzm B -/- NK cells
to induce apoptosis in susceptible targets in vitro. These in vivo data
define significant role for gzm B in cytotoxicity mediated by CD8+ CTL, but
not by CD4+ CTL. Furthermore, these results do not support a model of
hybrid resistance in which NK cells play a pivotal role.
Volume 87,
Issue 4,
pp. 1232-1237,
02/15/1996
Copyright © 1996 by The American Society of Hematology
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
J. A. Rotolo, B. Stancevic, S. X. Lu, J. Zhang, D. Suh, C. G. King, L. W. Kappel, G. F. Murphy, C. Liu, Z. Fuks, et al.
Cytolytic T cells induce ceramide-rich platforms in target cell membranes to initiate graft-versus-host disease
Blood,
October 22, 2009;
114(17):
3693 - 3706.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Mariotti, J. Foley, K. Ryan, N. Buxhoeveden, V. Kapoor, S. Amarnath, and D. H. Fowler
Graft rejection as a Th1-type process amenable to regulation by donor Th2-type cells through an interleukin-4/STAT6 pathway
Blood,
December 1, 2008;
112(12):
4765 - 4775.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Gorski, X. Chen, M. Gendelman, M. Yassai, A. Krueger, E. Tivol, B. Logan, R. Komorowski, S. Vodanovic-Jankovic, and W. R. Drobyski
Homeostatic expansion and repertoire regeneration of donor T cells during graft versus host disease is constrained by the host environment
Blood,
June 15, 2007;
109(12):
5502 - 5510.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Adrain, P. J. Duriez, G. Brumatti, P. Delivani, and S. J. Martin
The Cytotoxic Lymphocyte Protease, Granzyme B, Targets the Cytoskeleton and Perturbs Microtubule Polymerization Dynamics
J. Biol. Chem.,
March 24, 2006;
281(12):
8118 - 8125.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Vodanovic-Jankovic, P. Hari, P. Jacobs, R. Komorowski, and W. R. Drobyski
NF-{kappa}B as a target for the prevention of graft-versus-host disease: comparative efficacy of bortezomib and PS-1145
Blood,
January 15, 2006;
107(2):
827 - 834.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. A. Taylor, A. Panoskaltsis-Mortari, G. J. Freeman, A. H. Sharpe, R. J. Noelle, A. Y. Rudensky, T. W. Mak, J. S. Serody, and B. R. Blazar
Targeting of inducible costimulator (ICOS) expressed on alloreactive T cells down-regulates graft-versus-host disease (GVHD) and facilitates engraftment of allogeneic bone marrow (BM)
Blood,
April 15, 2005;
105(8):
3372 - 3380.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. T. N. Pham, J. L. Ivanovich, S. Z. Raptis, B. Zehnbauer, and T. J. Ley
Papillon-Lefevre Syndrome: Correlating the Molecular, Cellular, and Clinical Consequences of Cathepsin C/Dipeptidyl Peptidase I Deficiency in Humans
J. Immunol.,
December 15, 2004;
173(12):
7277 - 7281.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Couriel, R. Saliba, K. Hicks, C. Ippoliti, M. de Lima, C. Hosing, I. Khouri, B. Andersson, J. Gajewski, M. Donato, et al.
Tumor necrosis factor-{alpha} blockade for the treatment of acute GVHD
Blood,
August 1, 2004;
104(3):
649 - 654.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. B. Sugerman, S. B. Faber, L. M. Willis, A. Petrovic, G. F. Murphy, J. Pappo, D. Silberstein, and M. R. M. van den Brink
Kinetics of Gene Expression in Murine Cutaneous Graft-versus-Host Disease
Am. J. Pathol.,
June 1, 2004;
164(6):
2189 - 2202.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Sun, L. A. Welniak, A. Panoskaltsis-Mortari, M. J. O'Shaughnessy, H. Liu, I. Barao, W. Riordan, R. Sitcheran, C. Wysocki, J. S. Serody, et al.
Inhibition of acute graft-versus-host disease with retention of graft-versus-tumor effects by the proteasome inhibitor bortezomib
PNAS,
May 25, 2004;
101(21):
8120 - 8125.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. S. Morris, K. P. A. MacDonald, V. Rowe, D. H. Johnson, T. Banovic, A. D. Clouston, and G. R. Hill
Donor treatment with pegylated G-CSF augments the generation of IL-10-producing regulatory T cells and promotes transplantation tolerance
Blood,
May 1, 2004;
103(9):
3573 - 3581.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Komatsu, M. Mammolenti, M. Jones, R. Jurecic, T. J. Sayers, and R. B. Levy
Antigen-primed CD8+ T cells can mediate resistance, preventing allogeneic marrow engraftment in the simultaneous absence of perforin-, CD95L-, TNFR1-, and TRAIL-dependent killing
Blood,
May 15, 2003;
101(10):
3991 - 3999.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Johnson, L. Scorrano, S. J. Korsmeyer, and T. J. Ley
Cell death induced by granzyme C
Blood,
April 15, 2003;
101(8):
3093 - 3101.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z. Jiang, E. Podack, and R. B. Levy
Major histocompatibility complex-mismatched allogeneic bone marrow transplantation using perforin and/or Fas ligand double-defective CD4+ donor T cells: involvement of cytotoxic function by donor lymphocytes prior to graft-versus-host disease pathogenesis
Blood,
July 15, 2001;
98(2):
390 - 397.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. H. Hsieh and R. Korngold
Differential use of FasL- and perforin-mediated cytolytic mechanisms by T-cell subsets involved in graft-versus-myeloid leukemia responses
Blood,
August 1, 2000;
96(3):
1047 - 1055.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. R. Hill and J. L. M. Ferrara
The primacy of the gastrointestinal tract as a target organ of acute graft-versus-host disease: rationale for the use of cytokine shields in allogeneic bone marrow transplantation
Blood,
May 1, 2000;
95(9):
2754 - 2759.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Yasukawa, H. Ohminami, J. Arai, Y. Kasahara, Y. Ishida, and S. Fujita
Granule exocytosis, and not the Fas/Fas ligand system, is the main pathway of cytotoxicity mediated by alloantigen-specific CD4+ as well as CD8+ cytotoxic T lymphocytes in humans
Blood,
April 1, 2000;
95(7):
2352 - 2355.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Pan, T. Teshima, G. R. Hill, D. Bungard, Y. S. Brinson, V. S. Reddy, K. R. Cooke, and J. L.M. Ferrara
Granulocyte Colony-Stimulating Factor-Mobilized Allogeneic Stem Cell Transplantation Maintains Graft-Versus-Leukemia Effects Through a Perforin-Dependent Pathway While Preventing Graft-Versus-Host Disease
Blood,
June 15, 1999;
93(12):
4071 - 4078.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Wargnier, C. Lafaurie, S. Legros-Maida, J.-F. Bourge, F. Sigaux, M. Sasportes, and P. Paul
Down-regulation of Human Granzyme B Expression by Glucocorticoids. DEXAMETHASONE INHIBITS BINDING TO THE Ikaros AND AP-1 REGULATORY ELEMENTS OF THE GRANZYME B PROMOTER
J. Biol. Chem.,
December 25, 1998;
273(52):
35326 - 35331.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. R. Blazar, P. A. Taylor, A. Panoskaltsis-Mortari, and D. A. Vallera
Rapamycin Inhibits the Generation of Graft-Versus-Host Disease- and Graft-Versus-Leukemia-Causing T Cells by Interfering with the Production of Th1 or Th1 Cytotoxic Cytokines
J. Immunol.,
June 1, 1998;
160(11):
5355 - 5365.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. M. Krams, M. Hayashi, C. K. Fox, J. C. Villanueva, K. J. Whitmer, W. Burns, C. O. Esquivel, and O. M. Martinez
CD8+ Cells Are Not Necessary for Allograft Rejection or the Induction of Apoptosis in an Experimental Model of Small Intestinal Transplantation
J. Immunol.,
April 15, 1998;
160(8):
3673 - 3680.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. T. N. Pham, D. A. Thomas, J. D. Mercer, and T. J. Ley
Production of Fully Active Recombinant Murine Granzyme B in Yeast
J. Biol. Chem.,
January 16, 1998;
273(3):
1629 - 1633.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. M. Gardiner, A. O' Meara, and D. J. Reen
Differential Cytotoxicity of Cord Blood and Bone Marrow-Derived Natural Killer Cells
Blood,
January 1, 1998;
91(1):
207 - 213.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Shresta, P. Goda, R. Wesselschmidt, and T. J. Ley
Residual Cytotoxicity and Granzyme K Expression in Granzyme A-deficient Cytotoxic Lymphocytes
J. Biol. Chem.,
August 8, 1997;
272(32):
20236 - 20244.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Shresta, J. H. Russell, and T. J. Ley
Mechanisms Responsible for Granzyme B-Independent Cytotoxicity
Blood,
June 1, 1997;
89(11):
4085 - 4091.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
