chapter  13
32 Pages

Neuroimmune Interactions in the Pathogenesis of Allergic Asthma

Allergic asthma is characterized by chronic airway in£ammation that has been implied to have an important role in the development of airway hyperresponsiveness (AHR) and recurrent reversible airway obstruction. There is overwhelming evidence that Tcells play a central role in allergic asthma (1). Strong evidence supports the notion that T-helper 2 (Th2) cells orchestrate allergic in£ammation driven by e¡ector functions of B cells, mast cells, and eosinophils. Di¡erentiation of naive CD4þ Tcells (Th0) intoTh1 orTh2 cells determines whether an antigen will raise a cellular or a humoral immune response. Delivery of foreign antigens to mucosal surfaces, such as the pulmonary airways, has been shown to preferentially induce aTh2-mediated response. Both the expansion of Th2 memory cells during the secondary exposure to allergen and the commitment of naiveTcells toTh2 cells are required for the development of a Th2 immune response during allergic asthma. The availability of interleukin-12 (IL-12) and interferon-g (IFN-g) in contrast to IL-4 is decisive for the maturation of Th0 cells intoTh1 orTh2 cells (2). Sources of IL-12 and IFN-g are mainly macrophages and dendritic cells (DCs). Whereas cells responsible for the initial IL-4 production are less well de¢ned and apparently include naive T cells themselves (3). In addition, the presentation of inhaled antigen toT cells by local antigen-presenting cells (APCs) is a critical step in triggering the local immune response toward a Th1 or Th2 type of immunity. Increasing evidence suggests that an already deviated Th1orTh2 cell response

can be reversed or further enhanced depending on the type of APCs responsible for restimulation and the subsequent secondary immune response (4). In early observations a regulation of Th1 and Th2 immune responses by dendritic cells has been found (5). However, recent data demonstrate that DCs in the respiratory tracts are specialized for initiating aTh2 immunity at themucosal sites (6). By contrast, within the airways B cells do not appear to be essential as APCs, even though they support the induction and expansion of Th2 cells (7). Finally, the resident lung tissue macrophages play a pivotal role in initiating and development of a lung allergic immunity.They attenuate allergic in£ammation and AHR bymountingTh1responses in the bronchial mucosa that antagonizes Th2 responses to inhaled antigen (8). ThisTh1-promoting activity is an inherent property of lung macrophages and regulated by priming these cells with IFN-g.