|
|
Blood, 15 November 2003, Vol. 102, No. 10, pp. 3719-3726.
Prepublished online as a Blood First Edition Paper on July 31, 2003; DOI 10.1182/blood-2003-04-1075.
 Previous Article | Table of Contents | Next Article 
IMMUNOBIOLOGY
Cathepsin-B-dependent apoptosis triggered by antithymocyte globulins: a novel mechanism of T-cell depletion
Marie-Cécile Michallet,
Frederic Saltel,
Xavier Preville,
Monique Flacher,
Jean-Pierre Revillard , and
Laurent Genestier
From the Laboratoire d'Immunopharmacologie, Institut National de la Santé et de la Recherce Médicale (INSERM) U503 and INSERM U404, Centre d'Etudes et de Recherche en Virologie et Immunologie, Lyon; and the Laboratoire de Biologie Moléculaire et Cellulaire, UMR 5665 CNRS/ENS (Centre National de la Recherche Scientifique, l'Ecole Normale Supérieure) Lyon, France.
Antithymocyte globulins (ATGs), the immunoglobulin G (IgG) fraction of sera from rabbits or horses immunized with human thymocytes or T-cell lines, are used in conditioning regimens for bone marrow transplantation, in the treatment of acute graft-versus-host disease, in the prevention or treatment of acute rejection in organ transplantation, and in severe bone marrow aplasia. In nonhuman primates, ATGs induce rapid, dose-dependent, T-cell depletion in peripheral lymphoid tissues, where apoptotic cells can be demonstrated in T-cell zones. We show here that increasing ATG concentrations in vitro resulted in reduced lymphocyte proliferative responses, associated with a rapid increase in the percentage of apoptotic cells. Apoptosis did not require prior exposure to interleukin-2, nor did it result in CD178/CD95 or tumor necrosis factor/tumor necrosis factor receptor (TNF/TNF-R) interactions; it was therefore clearly different from activation-induced cell death. Cytochrome c release, caspase-9, and caspase-3 activation were not implicated, excluding a direct involvement of the intrinsic mitochondrial pathway. The cysteine protease inhibitor E64d and cathepsin-B-specific inhibitors conferred significant protection, whereas apoptosis was associated with the release of active cathepsin B into the cytosol. These data demonstrate a role for cathepsin B in T-cell apoptosis induced by ATGs at concentrations achieved during clinical use. (Blood. 2003; 102:3719-3726)
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
G. Simon, M. Parker, V. Ramiya, C. Wasserfall, Y. Huang, D. Bresson, R. F. Schwartz, M. Campbell-Thompson, L. Tenace, T. Brusko, et al.
Murine Antithymocyte Globulin Therapy Alters Disease Progression in NOD Mice by a Time-Dependent Induction of Immunoregulation
Diabetes,
February 1, 2008;
57(2):
405 - 414.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. D. LYTTON, C. P. DENTON, and A. M. NUTZENBERGER
Treatment of Autoimmune Disease with Rabbit Anti-T Lymphocyte Globulin: Clinical Efficacy and Potential Mechanisms of Action
Ann. N.Y. Acad. Sci.,
September 1, 2007;
1110(1):
285 - 296.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Loh, Y. Oyama, L. Statkute, K. Quigley, K. Yaung, E. Gonda, W. Barr, B. Jovanovic, R. Craig, D. Stefoski, et al.
Development of a secondary autoimmune disorder after hematopoietic stem cell transplantation for autoimmune diseases: role of conditioning regimen used
Blood,
March 15, 2007;
109(6):
2643 - 2548.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
U. Maitra, J. Seo, M. M. Lozano, and J. P. Dudley
Differentiation-Induced Cleavage of Cutl1/CDP Generates a Novel Dominant-Negative Isoform That Regulates Mammary Gene Expression
Mol. Cell. Biol.,
October 15, 2006;
26(20):
7466 - 7478.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Wang, N. Muller, K. G. McPherson, and H. M. Reichardt
Glucocorticoids Engage Different Signal Transduction Pathways to Induce Apoptosis in Thymocytes and Mature T Cells
J. Immunol.,
February 1, 2006;
176(3):
1695 - 1702.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. He, Y. Tohyama, K.-i. Yamamoto, M. Kobayashi, Y. Shi, T. Takano, C. Noda, K. Tohyama, and H. Yamamura
Lysosome is a primary organelle in B cell receptor-mediated apoptosis: an indispensable role of Syk in lysosomal function
Genes Cells,
January 1, 2005;
10(1):
23 - 35.
[Abstract]
[Full Text]
[PDF]
|
|
|
| |
