The studies proposed in this grant will examine the early steps in the pathogenesis of T-lymphocyte mediated central nervous system (CNS) immune reactions in the rat. Three areas will be studied in depth. These are: 1) The expansion of encephalitogenic cells in lymphoid tissue without the use of adjuvant. 2) Investigation of T-lymphocyte features (antigen specificity and MHC molecule expression) governing entry of T-cells to the CNS. And 3) Identification of the antigen presenting cell in the rat central nervous system. These studies will make extensive use of long- term T-cell lines and clones, immunohistochemistry, and bone marrow chimeras between rats susceptible and resistant to experimental allergic encephalomyelitis (EAE). The major scientific questions addressed by this series of experiments concern T-lymphocyte traffic in the nervous system. early features occurring following lymphocyte entry into the CNS. induction of MHC restriction molecules in the nervous system, and definition of a cell type or types with antigen presenting capabilities. This work should have direct relevance to central nervous system immunology in general and the human disease Multiple Sclerosis in particular.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS027321-02
Application #
3413570
Study Section
Neurology C Study Section (NEUC)
Project Start
1988-09-01
Project End
1991-08-31
Budget Start
1989-09-01
Budget End
1990-08-31
Support Year
2
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Washington University
Department
Type
Schools of Medicine
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Williams, Kenneth C; Hickey, William F (2002) Central nervous system damage, monocytes and macrophages, and neurological disorders in AIDS. Annu Rev Neurosci 25:537-62
Sweitzer, Sarah M; Hickey, William F; Rutkowski, Maria D et al. (2002) Focal peripheral nerve injury induces leukocyte trafficking into the central nervous system: potential relationship to neuropathic pain. Pain 100:163-70
Kielian, Tammy; van Rooijen, Nico; Hickey, William F (2002) MCP-1 expression in CNS-1 astrocytoma cells: implications for macrophage infiltration into tumors in vivo. J Neurooncol 56:1-12
Kielian, T; Barry, B; Hickey, W F (2001) CXC chemokine receptor-2 ligands are required for neutrophil-mediated host defense in experimental brain abscesses. J Immunol 166:4634-43
Hickey, W F (2001) Basic principles of immunological surveillance of the normal central nervous system. Glia 36:118-24
Ratcliffe, N R; Wegmann, K W; Zhao, R W et al. (2000) Identification and characterization of the antigen presenting cell in rat autoimmune myocarditis: evidence of bone marrow derivation and non-requirement for MHC class I compatibility with pathogenic T cells. J Autoimmun 15:369-79
Ratcliffe, N R; Hutchins, J; Barry, B et al. (2000) Chronic myocarditis induced by T cells reactive to a single cardiac myosin peptide: persistent inflammation, cardiac dilatation, myocardial scarring and continuous myocyte apoptosis. J Autoimmun 15:359-67
Yeager, M P; DeLeo, J A; Hoopes, P J et al. (2000) Trauma and inflammation modulate lymphocyte localization in vivo: quantitation of tissue entry and retention using indium-111-labeled lymphocytes. Crit Care Med 28:1477-82
Kielian, T; Hickey, W F (2000) Proinflammatory cytokine, chemokine, and cellular adhesion molecule expression during the acute phase of experimental brain abscess development. Am J Pathol 157:647-58
Williams, K C; Zhao, W; Politopoulou, G et al. (2000) Inhibition of experimental allergic encephalomyelitis with an antibody that recognizes a novel antigen expressed on lymphocytes, endothelial cells, and microglia. Lab Invest 80:313-26

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