We are studying the cellular and molecular basis of autoimmune diseases with two purposes. First, we want to establish the pathogenic role and antigen-specificity of T cells that cause autoimmune diseases such as multiple sclerosis, myasthenia gravis, insulin-dependent diabetes, among others. Second, we would like to determine the feasibility of specific antigen- induced apoptosis as a means of treating such autoimmune diseases. To these ends, we have made progress in the following areas: 1) we have successfully established the marmoset model of experimental allergic encephalomyelitis at the NIH; 2) we found that an important component of the marmoset disease is the formation of a pathogenic antibody against a protein component of the insulating sheath (myelin) of nerves in the central nervous system; 3) we are taking the first steps towards a clinical trial of antigen-induced apoptosis in multiple sclerosis, and 4) we are creating a transgenic mouse model of myasthenia gravis in order to test the efficacy of antigen-induced apoptosis. As part of these studies we are also trying to understand the regulation of antigen-induced death by T cell receptor stimulation. These studies should yield important new insights into the pathogenesis and treatment of autoimmune diseases which is a widespread health problem in the U.S. particularly among working women.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000717-04
Application #
6099042
Study Section
Special Emphasis Panel (LI)
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
1998
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code
Zheng, Lixin; Bidere, Nicolas; Staudt, David et al. (2006) Competitive control of independent programs of tumor necrosis factor receptor-induced cell death by TRADD and RIP1. Mol Cell Biol 26:3505-13
Zheng, Lixin; Lenardo, Michael (2006) T helper 2 cells' preferred way to die. Immunity 25:187-8
Deng, Guo-Min; Zheng, Lixin; Chan, Francis Ka-Ming et al. (2005) Amelioration of inflammatory arthritis by targeting the pre-ligand assembly domain of tumor necrosis factor receptors. Nat Med 11:1066-72
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Lobito, Adrian A; Yang, Bingzhi; Lopes, Marcela F et al. (2002) T cell receptor transgenic mice recognizing the immunodominant epitope of the Torpedo californica acetylcholine receptor. Eur J Immunol 32:2055-67
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Locksley, R M; Killeen, N; Lenardo, M J (2001) The TNF and TNF receptor superfamilies: integrating mammalian biology. Cell 104:487-501

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