Kevan Roberts

Allergic asthma is characterized by airway hyperresponsiveness and eosinophilic inflammation mediated by CD4+ Th2 cells. That these events arise as a consequence of a defect in immune regulation is implied from the observation that lung mucosal immune responses are normally tightly regulated. However, the specific mechanisms that transpires to resolve, or possibly prevent, airway mucosal Th2-mediated inflammation are poorly understood. Certainly, the production of specific prostanoids and the anti-inflammatory cytokines TGF-b or IL-10 at sites of inflammation serve to limit mucosal immune responses.

The laboratory focuses primarily on the regulation of lung mucosal Th2 responses. Most notably, we are elucidating how prostanoids such as PGI2, generated during allergic pulmonary inflammation, serve to selectively limit the progression of Th2 responses. In addition, we are investigating whether Th2-mediated airway inflammation is influenced by antigen-specific regulatory T cells. Regulatory T cells have been identified in mice and humans as a distinct population of CD4+ T cells that constitutively express the IL-2 receptor (IL-2R) a chain (CD25). CD4+CD25+ T cells play an essential role in the maintenance of peripheral self-tolerance by preventing the activation and proliferation of autoreactive T cells that have escaped thymic deletion. CD4+CD25+ T cells from DO11.10 mice express the transgenic T cell receptor and mediate regulatory activity. We have demonstrated that CD4+CD25+ T cells play a key role in regulating airway eosinophilic inflammation, most notably by limiting the differentiation of a specific proinflammatory CD4+ Th2 phenotype. An understanding of the regulation of Th2 responses will provide better insight into design of novel approaches to modulate the chronic airway inflammation evident in bronchial asthma.