Interactions Between the Human Immune System and Antigens in the Nervous System

McFarland, H F.

Abstract

The purpose of this project is to examine the manner in which immunological mechanisms may contribute to diseases of the central nervous system (CNS) in humans. These studies included examination of the cellular immune response to viruses which can commonly infect the CNS and which may be related to the induction of immunopathological processes of the nervous system. In addition, these studies have examined the immune response, and in particular, the cellular immune response to antigens of the nervous system such as myelin basic protein and proteolipid protein which may contribute to autoimmune disease. The emphasis in these studies has been on identifying differences which may occur in patients with diseases of the CNS, such as multiple sclerosis, as compared to healthy individuals. Particular attention has been paid to the influence of genetic makeup on both the induction and effector phases of the immune response to viruses, as well as antigens of the CNS. Focus has been placed on identification of cytotoxic T cells specific for both viruses or antigens of the nervous system.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Neurological Disorders and Stroke (NINDS)
• Type: Intramural Research (Z01)
• Project #: 1Z01NS002205-16
• Application #: 3860774
• Support Year: 16
• Fiscal Year: 1991

Institution

• Name: National Institute of Neurological Disorders and Stroke
• Country: United States

Publications

Lunemann, Jan D; Kamradt, Thomas; Martin, Roland et al. (2007) Epstein-barr virus: environmental trigger of multiple sclerosis? J Virol 81:6777-84

Martin, Roland; Bielekova, Bibiana; Hohlfeld, Reinhard et al. (2006) Biomarkers in multiple sclerosis. Dis Markers 22:183-5

Sospedra, Mireia; Muraro, Paolo A; Stefanova, Irena et al. (2006) Redundancy in antigen-presenting function of the HLA-DR and -DQ molecules in the multiple sclerosis-associated HLA-DR2 haplotype. J Immunol 176:1951-61

Cassiani-Ingoni, Riccardo; Cabral, Erik S; Lunemann, Jan D et al. (2006) Borrelia burgdorferi Induces TLR1 and TLR2 in human microglia and peripheral blood monocytes but differentially regulates HLA-class II expression. J Neuropathol Exp Neurol 65:540-8

Cassiani-Ingoni, Riccardo; Coksaygan, Turhan; Xue, Haipeng et al. (2006) Cytoplasmic translocation of Olig2 in adult glial progenitors marks the generation of reactive astrocytes following autoimmune inflammation. Exp Neurol 201:349-58

Bielekova, Bibiana; Catalfamo, Marta; Reichert-Scrivner, Susan et al. (2006) Regulatory CD56(bright) natural killer cells mediate immunomodulatory effects of IL-2Ralpha-targeted therapy (daclizumab) in multiple sclerosis. Proc Natl Acad Sci U S A 103:5941-6

Muraro, Paolo A; Cassiani-Ingoni, Riccardo; Chung, Katherine et al. (2006) Clonotypic analysis of cerebrospinal fluid T cells during disease exacerbation and remission in a patient with multiple sclerosis. J Neuroimmunol 171:177-83

Sospedra, Mireia; Martin, Roland (2006) Molecular mimicry in multiple sclerosis. Autoimmunity 39:3-8

Lunemann, Jan D; Edwards, Nancy; Muraro, Paolo A et al. (2006) Increased frequency and broadened specificity of latent EBV nuclear antigen-1-specific T cells in multiple sclerosis. Brain 129:1493-506

Cassiani-Ingoni, Riccardo; Greenstone, Heather L; Donati, Donatella et al. (2005) CD46 on glial cells can function as a receptor for viral glycoprotein-mediated cell-cell fusion. Glia 52:252-8