The study of the neuroantigen-specific CD4 T cells that mediate multiple sclerosis (MS) and its murine model, experimental allergic encephalomyelitis (EAE), continues to be challenging in vivo. Our knowledge of the contribution these cells make to the autoimmune disease process is particularly incomplete when it comes to an understanding of their function in the central nervous system 9CNS) itself. A primary goal of this application is to progress toward measuring their numbers and cytokine production (the primary effector function of CD4 T cells) in murine EAE models, in the CNS, and other compartments such as the blood and extra-lymphoid tissues.
In Aim 1 we propose to study the population kinetics of the autoimmune T cell response in the course of EAE measuring the numbers of T cells reactive to the neuroantigens MBP and PLP, or the foreign antigen, OVA, in various tissues including lymphoid tissues (lymph nodes, LN, and spleen), the blood, and the CNS at various time points after the disease inducing immunization. This will be done by ELISPOT analysis, by intracytoplasmatic staining, and by in situ hybridization for select cytokines. Our studies should shed light on the distribution of neuroantigen-specific T cells in the organism at various stages of the disease process and on the natural history of the dynamics and selection of the autoimmune T cell repertoire.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS039434-03
Application #
6529589
Study Section
Immunological Sciences Study Section (IMS)
Program Officer
Utz, Ursula
Project Start
2000-09-30
Project End
2005-08-31
Budget Start
2002-09-01
Budget End
2003-08-31
Support Year
3
Fiscal Year
2002
Total Cost
$260,100
Indirect Cost
Name
Case Western Reserve University
Department
Pathology
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
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Kuerten, Stefanie; Kostova-Bales, Dilyana A; Frenzel, Lukas P et al. (2007) MP4- and MOG:35-55-induced EAE in C57BL/6 mice differentially targets brain, spinal cord and cerebellum. J Neuroimmunol 189:31-40
Lichtenegger, Felix S; Kuerten, Stefanie; Faas, Susan et al. (2007) Dissociation of experimental allergic encephalomyelitis protective effect and allergic side reactions in tolerization with neuroantigen. J Immunol 178:4749-56
Hofstetter, Harald H; Toyka, Klaus V; Tary-Lehmann, Magdalena et al. (2007) Kinetics and organ distribution of IL-17-producing CD4 cells in proteolipid protein 139-151 peptide-induced experimental autoimmune encephalomyelitis of SJL mice. J Immunol 178:1372-8
Kuerten, Stefanie; Lichtenegger, Felix S; Faas, Susan et al. (2006) MBP-PLP fusion protein-induced EAE in C57BL/6 mice. J Neuroimmunol 177:99-111
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Quast, Stefan; Zhang, Wenji; Shive, Carey et al. (2005) IL-2 absorption affects IFN-gamma and IL-5, but not IL-4 producing memory T cells in double color cytokine ELISPOT assays. Cell Immunol 237:28-36