| Summary: | 碩士 === 國立陽明大學 === 微生物及免疫學研究所 === 105 === Abatacept is a cytotoxic T lymphocyte antigen-4 (CTLA-4) fusion protein approved for rheumatoid arthritis (RA) treatment worldwide. Abatacept is able to mimic the natural CTLA-4 and compete CD28 binding their ligands CD80/CD86 to prevent T cell activation. However, the reverse signals induced through the interaction of CTLA-4-Ig with CD80/CD86 on antigen-presenting cells (APCs) such as dendritic cells (DCs), macrophages and B cells are not fully understood. To test whether CTLA-4 regulates B cell functions, we assayed the effect of Abatacept on human B cells in both in vitro and in vivo conditions. In our study, we observed that Abatacept transiently reduced the level of CD80/CD86 on peripheral blood memory B cells and changed the naïve to memory B cell ratio. We measured several specific antibody levels in the serum from patients with RA before and after Abatacept treatment and observed a differential influence of Abatacept on these antibodies. In the in vitro assays, activation-induced B cell functions were suppressed by Abatacept in certain conditions but not in others. As expected, Abatacept suppressed Daudi B cells-induced allogeneic T cell proliferation, indicating a significant blockade of T-B interaction by Abatacept. Our results demonstrate a profound effect of Abatacept on both in vitro and in vivo B cell activities.
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