Atopic allergy and other hypersensitivities: Editorial overview Present and future trends in allergy

Abstract

As Kapsenberg and his colleagues (pp 788-793) have outlined, allergic diseases are associated with the presence of allergen-specific type2 T helper (Th2) cells. It is now clear that in man, as in the mouse, there are two types of helper cell. Thl and Th2 cells produce interleukin (IL)-2 and interferon-y and display cytotoxicity to antigen-presenting B cells, whereas Th2 cells produce IL-4 and IL-5 and provide helper function to B cells. The production of IL-4 by Th2 cells is critical for the IgE antibody response because IL-4 is the IgE switch factor. Kapsenberg addresses the complex and still unresolved issue of what determines the preponderance of Th2 versus Thl cells. The structure of antigen clearly plays a role. This is illustrated by the fact that all individuals regardless of their atopic background respond to antigens from helminthic parasites by making Th2 cells and by IgE isotype production. Furthermore, minute changes in the structure of certain peptides result in the switch from a preponderance of Thl to Th2 cells during an immune response. As would be expected from clinical observations heredity plays a major role in determining whether a Th2 response occurs to allergens. In this respect, experiments by various investigators have shown that atopic individuals make a Th2 response to allergens. The same allergens, when given to normal individuals, elicit only a Thl response. There is tantalizing evidence to suggest that prostaglandin production, which is selec tive to some antigen-presenting cells and which is elevated in individuals with atopy, plays an important role in determining the preponderance of Th2 cells. Indeed, prostaglandin E, and E2 as well as elevation of cyclic AMP, a downstream event of prostaglandin action, inhibit Thl cytokine production by Thl cells, i.e. inhibit interferon-y and IL-2 production, whereas production of IL-4 and IL-5 by Th2 cells is not affected. Remarkably, the bee venom allergen phospholipase A2 which is a potent inducer of prostaglandin synthesis elicits IgE antibod) responses both in allergic and non-allergic individuals. Whether a similar situation will be found in helminthic infections remains to be established.