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Dr. Scott's current research is focused on understanding the development, regulation and maintenance of CD4+ and CD8+ T cells in order to design new vaccines and immunotherapies for infectious diseases. The laboratory primarily focuses on experimental murine infections with the protozoan parasite, Leishmania, which provides a well-characterized model of T helper cell differentiation. The use of IL-12 as an adjuvant to promote Th1 cell development, as well as the ability of combined drug and IL-12 therapy to promote a Th2 to Th1 switch, was first shown in this laboratory. Both findings have implications for the control and treatment of infectious diseases, autoimmunity and allergy. While much has been learned about the development of Th1 cells, our understanding of how to maintain Th1 responses is limited. This is highlighted by the fact that there is no vaccine for human leishmaniasis. Dr. Scott's laboratory is investigating the role of cytokines, antigen-dose, CD8+ T cells and antigen persistence in the development of immunologic memory.
Another major interest in this laboratory is to better understand how different species of Leishmania interact with the host immune system, in order to develop new treatments for chronic leishmaniasis. For example, in contrast to L. major infections, infections with L. mexicana fail to resolve in C57BL/6 mice, and the lab has linked this phenotype to a defect in dendritic cell activation following infection. On the other hand, infections with L. braziliensis resolve in BALB/c mice, which are susceptible to both L. major and L. mexicana, and studies are underway to elucidate the factors that promote lesion resolution with this parasite. Most recently, the Scott lab has begun studies in Brazil with L. braziliensis patients. L. braziliensis can cause disfiguring chronic disease, in spite of the development of a strong immune response and control of the parasites. Thus, the disease is primarily due to immunopathology, including the production of high levels of TNF-a. One type of monocyte (termed proinflammatory monocytes) is known to produce high levels of TNF-a, and this subset is expanded in L. braziliensis patients. In collaboration with colleagues in Brazil, the Scott lab is looking at the how these monocytes are regulated during infection.