Dr. Bluestone ‘s lab has, for the last 20+ years, focused on the molecular and cellular aspects of T-cell activation, co-stimulation, and immune tolerance research. We have made significant advances in the understanding of T cell surface molecules that positively alter the signals delivered by the antigen-specific T cell receptor and the secondary co-stimulatory signals (such as CD28), as well as the negative regulatory events such as CTLA-4 and PD-1 that control T cell signal transduction essential for a homeostatic T cell response. While blockade of CD28 interactions with its ligands B7-1 and B7-2 induces long-term tolerance, the blockade of CTLA-4 interactions with the same B7 ligands exacerbates immunity. Importantly, our group has been at the forefront of clinical studies that have led to the development of multiple pro-tolerogenic immunotherapies including: CTLA4Ig (the first FDA-approved drug targeting T-cell co-stimulation to treat autoimmune disease and organ transplantation), a novel anti-human CD3 antibody being developed to treat Type 1 Diabetes (T1D), and the first CTLA-4 antagonist drugs approved for the treatment of metastatic melanoma.
In recent years, Dr. Bluestone’s work has focused on the critical role of regulatory T cells (Tregs) in autoimmunity. We have advanced the detailed understanding of the role of Tregs in the control immune homeostasis in type 1 diabetes and other autoimmune disease and organ transplant rejection. Importantly, our group has determined the key role of Treg stability in autoimmune settings. Clinically, our lab has spearheaded the use of Tregs as a cell-based therapy to treat T1D and transplantation emphasizing the ability to take scientific discoveries from the laboratory to the clinic.
Finally, the Bluestone lab continues efforts to combine immune tolerance therapies and islet cell transplantation. In programs performed in collaboration with UCSF and other stem cell programs, we have pursue efforts to combine human embryonic stem cell and iPS cell-derived islets with our tolerance studies to develop therapies that will lead to the treatment and cure of diabetes.