The long term objective of this project is to advance our understanding of self-tolerance and autoimmunity, emlpoying experimental allergic encephalomyelitis (EAE) in Lewis rats as a model.
The specific aims are as follows: 1. To ascertain how autoreactive cells can be activated in vivo to elicit autoimmune disease. We will use recipients of myelin- basic protein (BP) cultured spleen cells (SpC) from nonimmune donors for these studies. These recipients are """"""""primed for EAE but do not develop the disease. We will ascertain whether additional """"""""signals"""""""" (provided by adjuvant, antigen, or lymphokines) trigger these cells to induce EAE. 2. To study the cellular interactions which lead to EAE, relying on the use of monoclonal antibodies of known specificity and lymphokines (e.g., interleukin 2) in vitro to inhibit or augment the activation of the effector T cells which induce EAE. The therapeutic value of the monclonal antibodies will be explored. This has potential clinical relevance with respect to MS. 3. To confirm and extend our preliminary finding that suppressor cells which appear after recovery from EAE function via the inhibition of gamma interferon production by EAE effector cells. 4. To develop the chronic relapsing EAE (CREAE) model in the Lewis rat, study suppressor and effector cell function, and determine the role of different central nervous system antigens in this form of the disease. This may provide insight into the pathogenesis of MS.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS006985-22
Application #
3393513
Study Section
Immunological Sciences Study Section (IMS)
Project Start
1976-09-01
Project End
1992-08-31
Budget Start
1988-09-01
Budget End
1989-08-31
Support Year
22
Fiscal Year
1988
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

Showing the most recent 10 out of 21 publications