Anti-cardiolipin antibodies (aCL) of the IgG isotype are significantly associated with recurrent venous thromboses in patients with the antiphospholipid syndrome (APS). it is now widely accepted that the aCL antibodies that are present in the APS are actually directed against phospholipid-binding proteins, specifically 1beta2-Glycoprotein I (beta2GPI) and prothrombin. Since the presence of CD4+ T cells is generally required for production of IgG antibodies, perhaps CD4+ T cells with specificity for (beta2GPI may participate in the production of pathogenic aCL in APS. In this regard, I have recently shown that beta2GPI-specific T cells are present in APS patients. Moreover, co-culture of patient peripheral blood mononuclear cells (PBMCs) with beta2GPI results in the upregulation of monocyte procoagulant activity (PCA) and this is reliant on CD4+ T cells. in this context, the goal of the D and F funding is to generate short-term beta2GPI-specific T cell lines to determine their functional role in APS. The long-term goal is to generate monoclonal T cell lines specific to beta2GPI and use these cell lines as a tool to dissect the cellular aspects of the APS response.
The aims of this study are: 1. To generate short-term beta2GPI-specific CD4+ T call lines from APS patients 2. To study the functional activity of beta2GPI-specific CD4+ T cell lines on B cells and monocytes, and characterize the phenotypes of these T cells 3. To define epitopes for beta2GPI-specific T cell lines
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