Can persistent IgE responses be suppressed?

Abstract

Since the discovery ofIgE in the late 1960s (Ishizaka, Ishizaka & Hornbrook, 1966; Johansson & Bennich, 1967) several animal models have been developed to study the regulation of IgE. IgE responses in atopic people are typically long lived and can be maintained when they are no longer exposed to allergen as in hay fever patients outside the pollen season. Such responses have proved difficult to produce in most species, with the exception of mice, and after an initial burst of IgE when first immunized, the response generated is rapidly suppressed. The artificial induction of IgE responses in rodents has required the use of adjuvants such as aluminium hydroxide and Bordatella pertussis or concomitant nematode infection (Jarrett & Stewart, 1972). T cells play a central role in regulating IgE responses (Okumura & Tada, 197 la; Katona, Urban & Finkelman, 1988), and as well as providing help for IgE B cells, they are capable of suppressing both primary and secondary IgE responses (Okumura & Tada, 1971b; Holt, Batty & Turner, 1981a). Thus two opposing functions for T cells in IgE regulation can be seen. These effects are mediated at least in part by T cell-derived cytokines. High levels of interleukin-4 (IL-4) were found to potentiate IgE synthesis from lipopolysaccharide (LPS) stimulated murine B cells in vitro (Coffman & Carty, 1986) and this effect could be antagonized with interferon-gamma (IFN-y) (Snapper & Paul, 1987). Anti-IL-4 antibody (Finkelman et al., 1986, 1988a) or IFN-y (Finkelman et al., 1988b) both suppress antigen and Nippostrongylus braziliensis-induced IgE responses in vivo. With N. braziliensis infestation, IgE levels spontaneously decline following worm expulsion but similar effects were also seen with anti-IL-4 and IFN-y in Heligmosomoides polygyrusinfested mice, where the worm is not expelled and IgE levels do not fall (Finkelman et al., 1990). The secondary IgE response produced with antigen and Al(OH)3 was largely but not completely inhibited with anti-IL-4 (Finkelman et al., 1990); these investigators conclude that the role of IL-4 in the maintenance of an IgE response is to recruit