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dc.contributor.authorKhalil, Magi Magdi
dc.identifier.citationSource: Dissertation Abstracts International, Volume: 62-09, Section: B, page: 3962.;Advisors: Betty Diamond.
dc.description.abstractSystemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of autoantibodies targeted against nuclear antigens. Kidney disease is the most common cause of morbidity and mortality among SLE patients and manifests as a glomerulonephritis mediated by high affinity, T cell dependent antibodies that show preferential reactivity to double-stranded DNA (dsDNA). Altered T cell and antigen presenting cell (APC) function has long been postulated as contributing factors to the development of SLE. However, direct proof for their involvement has been lacking because the initiating antigens in the disease are not known.;We have developed an induced model of SLE in which non-autoimmune BALB/c mice immunized with a peptide mimetope of dsDNA on a branched poly-lysine backbone (DWEYSVWLSN-MAP) develop an SLE-like syndrome. The advantage of a known antigenic stimulus in this model has allowed us to explore T cell and APC contributions to disease mechanisms in lupus. Our results indicate that autoantibody production in this model requires the generation of a critical T cell epitope by APC. This T cell epitope requires the presence of both DWEYSVWLSN and the poly-lysine backbone, and does not derive from nuclear antigens, suggesting that SLE may arise through activation of T cells to foreign antigen and molecular mimicry at the B cell level. In addition, altered cytokine production by APC in BALB/c mice lacking gamma chain expression results in greater T cell activation, higher levels of anti-peptide and anti-dsDNA antibodies, and accelerated disease following DWEYSVWLSN-MAP immunization.;These studies have defined the antigenic specificity of the pathogenic T cells and the molecular basis for altered APC function in a peptide-induced model of SLE. The current treatment options for SLE are primarily palliative, with little specificity for the underlying disease. This model has provided a clearer understanding of the role of T cells and APC in the etiology of this complex disease, allowing for selective targeting of T cell and APC function in the design of therapeutic strategies for SLE.
dc.publisherProQuest Dissertations & Theses
dc.subjectCellular biology.
dc.titleCellular interactions in a peptide-induced model of systemic lupus erythematosus

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