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 characterized a transgenic T cell receptor mouse model of myasthenia gravis which has a powerful response to a peptide from the acetylcholine receptor; 2) we are studying sets of apoptosis-related genes for association with autoimmunity to establish genetic determinants of autoimmunity; and 3) we are initiating studies of antigen-specific therapy of immune thrombocytopenic purpura. 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 #
1Z01AI000717-07
Application #
6503204
Study Section
(LI)
Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
2001
Total Cost
Indirect Cost
Name
Niaid Extramural Activities
Department
Type
DUNS #
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
Lobito, Adrian A; Lopes, Marcela F; Lenardo, Michael J (2004) Ectopic T cell receptor expression causes B cell immunodeficiency in transgenic mice. Eur J Immunol 34:890-8
Miagkov, Alexei; Lobito, Adrain A; Yang, Bingzhi et al. (2003) Production and characterization of a T cell receptor transgenic mouse recognizing the immunodominant epitope of the Torpedo californica acetylcholine receptor. Ann N Y Acad Sci 998:379-83
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
Chamorro, M; Czar, M J; Debnath, J et al. (2001) Requirements for activation and RAFT localization of the T-lymphocyte kinase Rlk/Txk. BMC Immunol 2:3
Locksley, R M; Killeen, N; Lenardo, M J (2001) The TNF and TNF receptor superfamilies: integrating mammalian biology. Cell 104:487-501
Zheng, L; Schickling, O; Peter, M E et al. (2001) The death effector domain-associated factor plays distinct regulatory roles in the nucleus and cytoplasm. J Biol Chem 276:31945-52
Siegel, R M; Lenardo, M J (2001) To B or not to B: TNF family signaling in lymphocytes. Nat Immunol 2:577-8

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