Human basophils as effectors and immunomodulators of allergic inflammation and innate immunity

Abstract

Basophils have often stood in the shadow of their tissue–fixed mast cell counterparts which share some, common features, such as high–affinity IgE receptor expression and the ability to release histamine. That rodent mast cells produce a variety of pro–allergic and inflammatory cytokines has further added to the deception that basophils only play a minor role in allergic inflammation. Surprisingly, in humans, basophils, but not mast cells, appear to be the prime early producers of the Th2–type cytokines IL–4 and IL–13, which perform several crucial functions in initiating and maintaining allergic responses. This putative immunomodulatory role of basophils is supported further by their ability to express CD40 ligand, which, together with IL–4 and IL–13, serve as inductors of B–cell proliferation and class switching to IgE and IgG4. Moreover, human basophils are the main cellular source for rapid IL–4 generation, a mandatory requirement for the development of Th2 responses. Recent specific staining techniques have localised basophils in various tissues affected by allergic diseases and it appears likely, but remains to be proven, that the interaction of basophils, T cells and B cells at these sites propagate pro–allergic immune responses. Additionally, basophil activation is not restricted to antigen–specific IgE crosslinking but can be caused in non–sensitised individuals by parasitic antigens, plant lectins and viral superantigens binding to non–specific IgEs. Finally, the presence of novel IgE–independent receptor targets that cause trafficking and Th2 cytokine release from basophils further underlines their potential role in innate as well as adaptive immunity.