My laboratory has been interested in understanding the immunologic contexts that lead to CD4+ T cell unresponsiveness or anergy. During these investigations, we have found that a major operational mechanism of cellular immune unresponsiveness involves a T cell with suppressive capabilities. This T cell was formally identified in the early 1990s and has been termed a CD25+ T regulatory (Treg) cell.
Ongoing work in my laboratory has demonstrated a link between GRAIL, an anergy-related E3 ubiquitin ligase, and CD25+ Treg cells. CD25+ Treg cells are a subset of regulatory T cells with an anergic phenotype that suppress immune responses in an antigen-specific fashion by a poorly understood mechanism. We hypothesize that GRAIL is necessary for the optimal function of naturally occurring and induced CD25+ Treg cells. By understanding the molecular basis for suppressor function of CD25+ Treg cells, directed approaches can be developed for therapeutic alternatives to varied disease states that result from inappropriate adaptive immune responses.
A second line of investigation in my laboratory involves translational research with subjects that have allergic diseases. Allergic diseases are major public health problems in children and adults. Allergic diseases are initiated in early childhood by poorly understood mechanisms. Mouse models of allergic disease strongly implicate a role for CD25+ Treg cells in initiation, perpetuation and regulation of allergic inflammation. In contrast, studies in humans with allergic disease are limited. Investigations in the role of CD25+ Treg cells in allergic disease will improve our understanding of allergic inflammation and potentially lead to improved approaches to disease management and treatment.
- To elucidate the role of GRAIL in CD25+ Treg cell biological function.
- To characterize the expression of TLRs on naturally occurring and adaptive CD25+ Treg cells and investigate the effect of their engagement on CD25+ Treg cell biological function.
- To prospectively study the development and function of CD25+ Treg cells in a childhood cohort at increased risk for developing atopic disease.
- Flow Cytometry
- Real-time QPCR
- Cell Culture
- Retroviral and lentiviral production
- Animal models of in vivo tolerance
- CD25+ T regulatory cell functional assays (human and rodent)
- Confocal microscopy