Description of Research Expertise

Research Interests
T cells and cytokines in infectious disease
Host-pathogen interactions
Development of Th1 and Th2 cells
Memory T cells

Key words: parasites, Leishmania, T cells, Th1 cells, Th2 cells, memory T cells

Dr. Scott's current research is focused on understanding the development, regulation and maintenance of CD4+ Th1 and Th2 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-or cell-mediated immunity-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. These studies indicate that a population of lymph node homing memory T cells, which have been called central memory T cells, are generated during Leishmania infection, and can be maintained in the absence of parasites. Future studies are directed at determining how to increase this population of memory T cells following vaccination. In related experiments, this laboratory has demonstrated that a Leishmania mutant, which lacks phosphoglycans and fails to induce disease, is maintained in vivo and protects mice against challenge with virulent organisms. Studies are in progress to characterize the immunity induced by these mutant parasites. Finally, studies are ongoing to understand how different species of Leishmania influence T helper cell subset development. While L. major induces a Th1 response and a healing infection in many strains of mice, the same strains of mice infected with parasites belonging to the L. mexicana complex fail to develop a Th1 response or heal. Thus, the laboratory is focused on defining the parasite virulence factors that modulate T helper cell development by different species of Leishmania.

Rotation Projects for 2007-2008
Lab rotation projects will involve studies related to:
• Th1 or Th2 cell development following infection with Leishmania major
• Studies of memory T cell development and maintenance
• Studies that define differences in Leishmania species that influence the nature of the immune response.

Leanne Johnson- graduate student IGG
Lucas Carvalho--Postdoctoral Fellow
Nazzy Pakpour- graduate student CAMB
Alice Hsu- graduate student IGG
Sara Colpitts- graduate student IGG
Carlos Rodriguez--Lab Manager