Supervisor View Full Details 2nd

• infectious disease and the immune system

• Medicine
• Paediatrics

• Infectious diseases
• Immunology

My group was the first to define a role for cellular immunity in protection against Bordetella pertussis. We defined protective roles for Th1 cells and subversive roles for Treg cells, published in J. Exp Med, and J. Immunol, and Nature Reviews Immunology. We provided the first definitive evidence that cellular immunity mediated by Th1 cells and Th17 plays a critical role natural immunity to B. pertussis. We demonstrated that infection of children with B. pertussis induced antigen-specific Th1 cells. We were also the first to describe pathogen-specific regulatory T cells in infection and that these cells constrain protective immunity to B. pertussis. More recently we have identified a role for lung tissue resident memory T cells in sustaining immunity to B. pertussis

Our work in autoimmune diseases demonstrated a key role for TLR-induced IL-1 and IL-23 in IL-17 production by T cells and a key pathogenic role for gamma-delta T cells. Our J. Exp Med article showed that IL-1 plays an essential role in IL-17 production by Th17 cells that are pathogenic in autoimmune diseases. Our Immunity paper provided the first evidence that γδ T cells play a pathogenic role in autoimmune disease through IL-17 production driven by innate cytokines.

The immune system utilizes a combination of cells, including T and B cells, and their secreted cytokines, to control infection. T cells, called γδ T cells and Th17 cells, which produce the cytokine IL-17 are important in the control of infection, however, they are also responsible for mediating pathology in many autoimmune diseases. T cells are classically recognized as distinct subsets that express αβ or γδ TCRs, we identified a novel population of T cells in mice defined by the co-expression of αβ and γδ TCRs. These hybrid αβ-γδ T cells expressed high are enriched for various chemokine receptors and homing molecules, facilitating migration to sites of inflammation, where they promoted bacterial clearance after infection with Staphylococcus aureus and played a key role in the development of autoimmune disease in the central nervous system. The proposed project will focus on identifying and characterizing a corresponding cell type in humans. The initial focus will be on peripheral blood cells from healthy donors, and will then progress to studies on samples from patients with infection; e.g. lung lavage samples from TB patients or liver biopsies from hepatitis C virus infected individuals.