The objective of this project is to elucidate the mechanisms that govern the induction and regulation of autoimmunity, using experimental allergic encephalomyelitis (EAE) as a model. Specifically, we will continue studies of EAE induced without adjuvant by culturing spleen or peritoneal cells from nonimmune Lewis rats with myelin basic protein. Although these cultured cells do not induce EAE following transfer to syngeneic primary recipients, when spleen cells from these recipients are cultured with basis protein they transfer EAE to secondary recipients. The production of EAE without adjuvant using antigen-cultured cells from naive donors may provide a clearer understanding of the mechanisms of autoimmune disease induction. We will determine whether natural suppressor cells in the primary recipients of antigen-cultured cells prevent these animals from developing EAE. We will study the triggering events that lead to autoimmune disease without the drawbacks previously associated with the use of adjuvants. We will also study the cellular interactions involved in the induction of EAE, characterize the relevant cell populations and cell-derived factors, and begin to elucidate the effector mechanisms of EAE. Since EAE serves as a prototype for human demyelinating diseases such as multiple sclerosis, this investigation should provide insight into the etiology of these disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS006985-20
Application #
3393512
Study Section
Immunological Sciences Study Section (IMS)
Project Start
1976-09-01
Project End
1987-08-31
Budget Start
1986-09-01
Budget End
1987-08-31
Support Year
20
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Wayne State University
Department
Type
Schools of Medicine
DUNS #
City
Detroit
State
MI
Country
United States
Zip Code
48202
Kheradmand, Taba; Trivedi, Prachi P; Wolf, Norbert A et al. (2008) Characterization of a subset of bone marrow-derived natural killer cells that regulates T cell activation in rats. J Leukoc Biol 83:1128-35
Wolf, Norbert A; Amouzegar, Taba K; Swanborg, Robert H (2007) Synergistic interaction between Toll-like receptor agonists is required for induction of experimental autoimmune encephalomyelitis in Lewis rats. J Neuroimmunol 185:115-22
Trivedi, Prachi P; Roberts, Paul C; Wolf, Norbert A et al. (2005) NK cells inhibit T cell proliferation via p21-mediated cell cycle arrest. J Immunol 174:4590-7
Conant, Stephanie B; Swanborg, Robert H (2004) Autoreactive T cells persist in rats protected against experimental autoimmune encephalomyelitis and can be activated through stimulation of innate immunity. J Immunol 172:5322-8
Conant, Stephanie B; Swanborg, Robert H (2003) MHC class II peptide flanking residues of exogenous antigens influence recognition by autoreactive T cells. Autoimmun Rev 2:8-12
Wolf, N A; Swanborg, R H (2001) DA rat NK(+)CD3(-) cells inhibit autoreactive T-cell responses. J Neuroimmunol 119:81-7
Lenz, D C; Swanborg, R H (1999) Suppressor cells in demyelinating disease: a new paradigm for the new millennium. J Neuroimmunol 100:53-7
Smeltz, R B; Wolf, N A; Swanborg, R H (1999) Inhibition of autoimmune T cell responses in the DA rat by bone marrow-derived NK cells in vitro: implications for autoimmunity. J Immunol 163:1390-7
Smeltz, R B; Swanborg, R H (1998) Concordance and contradiction concerning cytokines and chemokines in experimental demyelinating disease. J Neurosci Res 51:147-53
Smeltz, R B; Wolf, N A; Swanborg, R H (1998) Delineation of two encephalitogenic myelin basic protein epitopes for DA rats. J Neuroimmunol 87:43-8

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