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Citations to this article

Mechanisms of drug-induced lupus. II. T cells overexpressing lymphocyte function-associated antigen 1 become autoreactive and cause a lupuslike disease in syngeneic mice.
R Yung, … , N Hemati, B Richardson
R Yung, … , N Hemati, B Richardson
Published June 15, 1996
Citation Information: J Clin Invest. 1996;97(12):2866-2871. https://doi.org/10.1172/JCI118743.
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Mechanisms of drug-induced lupus. II. T cells overexpressing lymphocyte function-associated antigen 1 become autoreactive and cause a lupuslike disease in syngeneic mice.

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Abstract

Current theories propose that systemic lupus erythematosus develops when genetically predisposed individuals are exposed to certain environmental agents, although how these agents trigger lupus is uncertain. Some of these agents, such as procainamide, hydralazine, and UV-light inhibit T cell DNA methylation, increase lymphocyte function-associated antigen 1 (LFA-1) (CD11a/CD18) expression, and induce autoreactivity in vitro, and adoptive transfer of T cells that are made autoreactive by this mechanism causes a lupuslike disease. The mechanism by which these cells cause autoimmunity is unknown. In this report, we present evidence that LFA-1 overexpression is sufficient to induce autoimmunity. LFA-1 overexpression was induced on cloned murine Th2 cells by transfection, resulting in autoreactivity. Adoptive transfer of the transfected, autoreactive cells into syngeneic recipients caused a lupuslike disease with anti-DNA antibodies, an immune complex glomerulonephritis and pulmonary alveolitis, similar to that caused by cells treated with procainamide. These results indicate that agents or events which modify T cell DNA methylation may induce autoimmunity by causing T cell LFA-1 overexpression. Since T cells from patients with active lupus have hypomethylated DNA and overexpressed LFA-1, this mechanism could be important in the development of human autoimmunity.

Authors

R Yung, D Powers, K Johnson, E Amento, D Carr, T Laing, J Yang, S Chang, N Hemati, B Richardson

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WJ Pichler
Current Opinion in Allergy and Clinical Immunology 2003
Combining Fas Mutation with Interleukin-2 Deficiency Prevents Colitis and Lupus: IMPLICATING INTERLEUKIN-2 FOR AUTO-REACTIVE T CELL EXPANSION AND Fas LIGAND FOR COLON EPITHELIAL CELL DEATH
S Xiao, SJ Sung, SM Fu, ST Ju
The Journal of biological chemistry 2003
DNA methylation in systemic lupus erythematosus
I Sekigawa, M Okada, H Ogasawara, H Kaneko, T Hishikawa, H Hashimoto
Lupus 2003
CD49d Overexpression and T Cell Autoimmunity
RR Mo, JK Eisenbraun, J Sonstein, RA Craig, JL Curtis, LM Stoolman, J Chen, RL Yung
Journal of immunology (Baltimore, Md. : 1950) 2003
Age-dependent DNA methylation changes in the ITGAL (CD11a) promoter
Z Zhang, C Deng, Q Lu, B Richardson
Mechanisms of Ageing and Development 2002
Drug-induced lupus as a cause of relapsing inflammatory disease after renal transplantation
L Pape, J Strehlau, K Latta, JH Ehrich, G Offner
Pediatric Transplantation 2002
Th2-type immunopathological manifestations induced by mercury chloride or gold salts in the rat: signal transduction pathways, cellular mechanisms and genetic control
GJ Fournié, A Saoudi, P Druet, L Pelletier
Autoimmunity Reviews 2002
Les lupus induits par les médicaments
J Sibilia
Revue du Rhumatisme 2002
Pathogenesis of lupus
K Oelke, B Richardson
Arthritis & Rheumatism 2002
Role of DNA Methylation in the Regulation of Cell Function: Autoimmunity, Aging and Cancer
BC Richardson
The Journal of nutrition 2002
Effect of DNA methylation and chromatin structure onITGAL expression
Q Lu, D Ray, D Gutsch, B Richardson
Blood 2002
Frequency of appearance of myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) in Graves' disease patients treated with propylthiouracil and the relationship between MPO-ANCA and clinical manifestations
JY Noh, T Asari, N Hamada, F Makino, N Ishikawa, Y Abe, K Ito, K Ito
Clinical Endocrinology 2001
Autoreactive murine Th1 and Th2 cells kill syngeneic macrophages and induce autoantibodies
R Yung, M Kaplan, D Ray, K Schneider, RR Mo, K Johnson, B Richardson
Lupus 2001
MHC Class II Associations with Autoantibody and T cell Immune Responses to the Scleroderma Autoantigen Topoisomerase I
AL Rands, J Whyte, B Cox, ND Hall, NJ McHugh
Journal of Autoimmunity 2000
Regulatory Defects in Cbl and Mitogen-Activated Protein Kinase (Extracellular Signal-Related Kinase) Pathways Cause Persistent Hyperexpression of CD40 Ligand in Human Lupus T Cells
Y Yi, M McNerney, SK Datta
Journal of immunology (Baltimore, Md. : 1950) 2000
TRAIL (Apo2 Ligand) and TWEAK (Apo3 Ligand) Mediate CD4 + T Cell Killing of Antigen-Presenting Macrophages
MJ Kaplan, D Ray, RR Mo, RL Yung, BC Richardson
Journal of immunology (Baltimore, Md. : 1950) 2000
Genetic dissection of lupus pathogenesis: a recipe for nephrophilic autoantibodies
C Mohan, L Morel, P Yang, H Watanabe, B Croker, G Gilkeson, EK Wakeland
Journal of Clinical Investigation 1999
Major peptide autoepitopes for nucleosome-specific T cells of human lupus
L Lu, A Kaliyaperumal, DT Boumpas, SK Datta
Journal of Clinical Investigation 1999
Environmentally induced autoimmune diseases: potential mechanisms
T Rao, B Richardson
Environmental Health Perspectives 1999
Role of DNA methylation in the regulation of cell function
B Richardson, R Yung
Journal of Laboratory and Clinical Medicine 1999
Lupus-like nephrotropic autoantibodies in non-autoimmune mice harboring an anti-basement membrane\anti-DNA Ig heavy chain transgenefn2fn2This work was supported in part by the Lupus Foundation of Delaware Valley, National Institutes of Health Grant DK47424 (M.H.F.), a George M. O’Brien Kidney and Urologic Research Center Grant DK45191, nih Training Grant DK07006, the Research Foundation of the University of Pennsylvania and the dci-red Fund
MH Foster, MM Fitzsimons
Molecular Immunology 1998
B-cell epitope spreading in autoimmunity
JA James, JB Harley
Immunological Reviews 1998
1 Immunopathogenesis of SLE
LJ Mason, DA Isenberg
Baillière's Clinical Rheumatology 1998
Differential Expression of T-Cell Adhesion Molecules and LFA-1-Dependent Intercellular Adhesion in HgCl2-Induced Autoimmunity and Immune Suppression
Roos, Claessen, Schilder-Tol, Weening, Aten
Scandinavian Journal of Immunology 1998
DRUG-INDUCED AUTOIMMUNE DISORDERS
K Krohn, R Bennett
Immunology and Allergy Clinics of North America 1998
Mechanisms of drug-induced lupus: III. Sex-specific differences in T cell homing may explain increased disease severity in female mice
R Yung, R Williams, K Johnson, C Phillips, L Stoolman, S Chang, B Richardson
Arthritis & Rheumatism 1997
Mechanisms of drug-induced lupus. III. Sex-specific differences in T cell homing may explain increased disease severity in female mice
R Yung, R Williams, K Johnson, C Phillips, L Stoolman, S Chang, B Richardson
Arthritis & Rheumatism 1997
Mechanisms of drug-induced lupus. IV. Comparison of procainamide and hydralazine with analogs in vitro and in vivo
R Yung, S Chang, N Hemati, K Johnson, B Richardson
Arthritis & Rheumatism 1997
Zinc-controlled Th1/Th2 switch significantly determines development of diseases
JE Sprietsma
Medical Hypotheses 1997
Advances in Pharmacology
B Drenger, Y Ginosar, Y Gozal
Advances in Pharmacology 1994
Rheumatology
RA Asherson, R Cervera, DP D'Cruz, GR Hughes
Postgraduate medical journal 1991

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