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Impaired Caspase-3 Expression By Peripheral T Cells In Chronic Autoimmune Thyroiditis And In Autoimmune Polyendocrine Syndrome-2.

F. Vendrame, M. Segni, D. Grassetti, V. Tellone, G. Augello, V. Trischitta, M. Torlontano, F. Dotta
Published 2006 · Medicine

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CONTEXT Activation-induced cell death (AICD) is a major mechanism in the regulation of peripheral tolerance, and caspase-3 represents its major executioner. AICD impairment contributes to the persistence of autoreactive T cells, and defective AICD has been reported in autoimmune thyroiditis as well as in type 1 diabetes mellitus. OBJECTIVE The objective of this study was to evaluate the involvement of caspase-3 in the regulation of AICD resistance in thyroid and polyendocrine autoimmunity. DESIGN/SETTINGS/PATIENTS/INTERVENTION: Caspase-3 expression was analyzed in peripheral blood lymphocytes from 26 adults (A-AT) and 25 children (Y-AT) affected by autoimmune thyroiditis and 13 individuals affected by chronic autoimmune thyroiditis plus Addison's disease [autoimmune polyendocrine syndrome-2 (APS-2)] in comparison with 32 age-matched normal control subjects (NC). OUTCOME MEASURES Caspase-3 mRNA expression in peripheral T cells was evaluated by quantitative real-time PCR; protein expression of both procaspase-3 and activated caspase-3 by Western blot analysis was followed by scanning densitometry. RESULTS Caspase-3 mRNA expression was significantly reduced in resting lymphocytes from both A-AT (P = 0.001) and Y-AT (P = 0.016) compared with NC. After lymphocyte activation, protein levels of caspase-3 active form were significantly reduced in A-AT (P = 0.023) and Y-AT (P = 0.001) compared with NC. The APS-2 group displayed characteristics similar to the A-AT group because both caspase-3 mRNA and protein active form levels were significantly reduced compared with NC (P = 0.004 and 0.002, respectively). CONCLUSION Our data show that peripheral lymphocytes of subjects affected by thyroid autoimmunity or APS-2 show defective expression of the major executioner of AICD, thus potentially contributing to AICD resistance and to the development of autoimmunity.
This paper references
10.1046/j.1365-2249.2003.02221.x
Defective function of Fas in T cells from paediatric patients with autoimmune thyroid diseases
G. Bóna (2003)
10.3109/08830189909088499
Apoptosis in human autoimmune diseases.
C. Ravirajan (1999)
10.1034/j.1600-065X.2003.00046.x
Caspases and T lymphocytes: a flip of the coin?
S. Lakhani (2003)
10.1034/j.1600-065X.2003.00047.x
The role of CD95 in the regulation of peripheral T‐cell apoptosis
A. Krueger (2003)
10.1101/GAD.12.6.806
Essential contribution of caspase 3/CPP32 to apoptosis and its associated nuclear changes.
M. Woo (1998)
Increased apoptosis of T cell subsets in aging humans: altered expression of Fas (CD95), Fas ligand, Bcl-2, and Bax.
S. Aggarwal (1998)
10.1146/ANNUREV.BIOCHEM.68.1.383
Mammalian caspases: structure, activation, substrates, and functions during apoptosis.
W. Earnshaw (1999)
10.1038/82725
Control of target cell survival in thyroid autoimmunity by T helper cytokines via regulation of apoptotic proteins
G. Stassi (2000)
10.1016/S0165-5728(00)00443-4
Overexpression of the apoptosis inhibitor FLIP in T cells correlates with disease activity in multiple sclerosis
Yemane K. Semra (2001)
10.1530/EJE.1.01813
Defective lymphocyte caspase-3 expression in type 1 diabetes mellitus.
F. Vendrame (2005)
10.1038/nri750
Autoimmune thyroid disease: new models of cell death in autoimmunity
G. Stassi (2002)
10.1038/227680A0
Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4
U. Laemmli (1970)
10.1074/jbc.272.8.4680
Energy Metabolism during Apoptosis
J. Garland (1997)
10.1023/A:1009692902805
Role of apoptosis in autoimmunity
H-M. Lorenz (2004)
10.1038/376037A0
Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis
D. Nicholson (1995)
10.1016/S0165-5728(01)00464-7
Disease activity in multiple sclerosis correlates with T lymphocyte expression of the inhibitor of apoptosis proteins
Yemane K. Semra (2002)
10.1038/373441A0
Cell-autonomous Fas (CD95)/Fas-ligand interaction mediates activation-induced apoptosis in T-cell hybridomas
T. Brunner (1995)
10.1016/S0952-7915(02)00335-7
Molecular mechanisms of activated T cell death in vivo.
David A Hildeman (2002)
10.1074/jbc.M008363200
Executioner Caspase-3, -6, and -7 Perform Distinct, Non-redundant Roles during the Demolition Phase of Apoptosis*
E. Slee (2001)
10.1084/jem.20032158
Defective Suppressor Function of Human CD4+ CD25+ Regulatory T Cells in Autoimmune Polyglandular Syndrome Type II
M. Kriegel (2004)
10.1056/NEJMOA040036
Autoimmune lymphoproliferative syndrome with somatic Fas mutations.
Eliska Holzelova (2004)
10.1034/j.1600-065X.2003.00051.x
Activation‐induced cell death in T cells
D. Green (2003)
10.1074/jbc.274.43.30651
Caspase-3 Is the Primary Activator of Apoptotic DNA Fragmentation via DNA Fragmentation Factor-45/Inhibitor of Caspase-activated DNase Inactivation*
Beni B Wolf (1999)
10.1038/373438A0
Autocrine T-cell suicide mediated by APO-1/(Fas/CD95)
J. Dhein (1995)
10.1126/SCIENCE.275.5302.960
Potential Involvement of Fas and Its Ligand in the Pathogenesis of Hashimoto's Thyroiditis
C. Giordano (1997)
10.1084/JEM.190.12.1891
Caspase Activation Is Required for T Cell Proliferation
N. Kennedy (1999)
10.1074/JBC.M006391200
Interleukin-3 Withdrawal Induces an Early Increase in Mitochondrial Membrane Potential Unrelated to the Bcl-2 Family
A. Khaled (2001)



This paper is referenced by
10.1074/jbc.M110.184523
Manganese Binds to Clostridium difficile Fbp68 and Is Essential for Fibronectin Binding*
Y. Lin (2010)
10.4067/S0034-98872012000900002
[Decreased caspase 3 expression and cytotoxic T lymphocyte antigen-4 polymorphism in Chilean patients with type 1 diabetes].
Bárbara Angel (2012)
10.1016/j.humimm.2012.04.020
High glucose concentration in T1D patients modulates apoptotic protein expression: down regulation of BAX and FAS and up regulation of XIAP.
Elizabeth Valencia (2012)
10.1016/j.jaut.2010.07.001
21-Hydroxylase epitopes are targeted by CD8 T cells in autoimmune Addison's disease.
D. Rottembourg (2010)
10.1111/j.1365-2796.2009.02091.x
Autoimmune polyendocrine syndrome type 1 (APS‐1) as a model for understanding autoimmune polyendocrine syndrome type 2 (APS‐2)
A. Michels (2009)
Glucocorticoid Treatment and Quality of Life in Addison’s disease
M. Øksnes (2014)
10.1172/JCI37878
IL-21 drives secondary autoimmunity in patients with multiple sclerosis, following therapeutic lymphocyte depletion with alemtuzumab (Campath-1H).
J. Jones (2009)
10.4067/S0034-98872009000500003
Association of GHRd3 variant of growth hormone receptor gene with autoimmunity in type 1 diabetes
D. DiegoGarcía (2009)
10.2337/db10-1620
Response to Comment on: Meagher et al. Neutralization of Interleukin-16 Protects Nonobese Diabetic Mice From Autoimmune Type 1 Diabetes by a CCL4-Dependent Mechanism. Diabetes 2010;59:2862–2871
C. Meagher (2011)
10.1097/MED.0b013e32836313eb
Insights into type 1 diabetes from the autoimmune polyendocrine syndromes
M. Cheng (2013)
10.1016/j.ecl.2009.01.007
Diagnosis and management of polyendocrinopathy syndromes.
C. Owen (2009)
10.1080/08916930902828163
Cells induced to undergo apo in the presence of the caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone stimulate Mo derived phagocytes to secrete proinflammatory cytokines
P. Heyder (2009)
10.2337/db10-1489
Comment on: Meagher et al. Neutralization of Interleukin-16 Protects Nonobese Diabetic Mice From Autoimmune Type 1 Diabetes by a CCL4-Dependent Mechanism. Diabetes 2010;59:2862–2871
F. Vendrame (2011)
10.1016/j.beem.2008.09.004
Pathogenesis of primary adrenal insufficiency.
E. Husebye (2009)
10.1586/eem.09.20
Recent advances in adrenal autoimmunity
A. Falorni (2009)
10.1111/j.1365-3083.2011.02630.x
In Type 1 Diabetes Immunocompetent Cells are Defective in IL‐16 Secretion
F. Vendrame (2012)
10.1080/08916930701356911
Attraction of phagocytes by apoptotic cells is mediated by lysophosphatidylcholine
R. Mueller (2007)
10.1504/IJLR.2010.032771
A new approach to individual prognostication of cancer development under conditions of chronic radiation exposure
Galina A. Veremeyeva (2010)
10.1016/j.immuni.2010.03.016
Autoimmune polyendocrine syndromes: clues to type 1 diabetes pathogenesis.
E. Husebye (2010)
10.1016/B978-0-7020-4087-0.00050-4
Neurologic complications of disorders of the adrenal glands.
T. Bertorini (2014)
10.4142/jvs.2008.9.2.133
The C-terminal variable domain of LigB from Leptospira mediates binding to fibronectin
Y. Lin (2008)
10.1016/j.clim.2008.06.015
A locus on chromosome 1 promotes susceptibility of experimental autoimmune myocarditis and lymphocyte cell death.
D. Ligons (2009)
10.1007/s13631-014-0063-1
Autoanticorpi anti-surrene nell’insufficienza corticosurrenalica primitiva
A. Brozzetti (2014)
10.1136/jcp.2010.086553
Changes of B and T lymphocytes and selected apopotosis markers in Hashimoto's thyroiditis
E. Kaczmarek (2011)
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