Project Details
Description
Experimental autoimmune encephalomyelitis (EAE) is a T cell-mediated inflammatory demyelinating disease of the CNS that serves as a model for human multiple sclerosis (MS). In the SJL/J mice, a relapsing-remitting form of EAE (R-EAE) is induced following active immunization with proteolipid protein (PLP), myelin basic protein (MBP), or the immunodominant epitopes on these molecules (PLP139-151 or MBP84-104) or following the adoptive transfer of peptide-specific Th1 cells. Based on the relapsing-remitting course of the disease, along with our finding that disease progression (relapses) in these peptide-induced R- EAE models are due primarily to the recruitment of T cell responses against non-crossreactive endogenous myelin epitopes on the same or different myelin proteins (intramolecular or intermolecular epitope spreading), we hypothesize that disease remission results from specific form(s) of immunoregulation. Specific Aim 1 of current proposal will build on our productive studies from the previous funding period to further delineate the role of several overlapping immunoregulatory mechanisms which appear to function in ameliorating CNS responses to the disease initiating epitopes leading to initiation of disease remission. These include: a switch of CNS cytokines from pro-inflammatory to anti-inflammatory (i.e., a Th1/Th2 switch) and/or the possible activation of antigen- or TcR-specific regulatory T cell populations in response to the disease-initiating T cells. Secondly, we will continue to elucidate the mechanisms responsible for downregulation of disease induction and progression following extrinsic induction of antigen-specific peripheral tolerance induced by the i.v. injection of protein/peptide-pulsed, ethylene carbodiimide (ECDI)-fixed antigen presenting cells (Ag-SP). In comparison to tolerance induced by the i.v. or oral administration of soluble peptide, tolerance induced by Ag-SP was shown to be highly effective for prevention and treatment of R-EAE, a
Status | Finished |
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Effective start/end date | 8/15/01 → 7/31/06 |
Funding
- National Institute of Neurological Disorders and Stroke (5 R01 NS026543-17)
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