DIFFERENCES BETWEEN IL-4R-ALPHA-DEFICIENT AND IL-4-DEFICIENT MICE REVEAL A ROLE FOR IL-13 IN THE REGULATION OF TH2 RESPONSES

Allergens and infections with parasitic helminths preferentially induc e Th2 immune responses associated with elevated levels of serum immuno globulin E (IgE) and expansion of eosinophils and mast cells. Interleu kin-4 (IL-4) is a key cytokine in the differentiation of naive CD4(+) T cells into Th2 cells, which produce a panel of cytokines including I L-4, IL-5, IL-6, IL-9, IL-10, and IL-13 [1] and have been shown to tri gger recovery from gastrointestinal nematodes [2], Nonetheless, mice d eficient for IL-4 have been shown to develop residual Th2 responses [3 -5] and can expel the nematode Nippostrongylus brasiliensis [6], sugge sting that there is a functional equivalent of IL-4 in these processes . IL-13 is a cytokine that shares some, but not all, biological activi ties with IL-4 [7,8]. There is now compelling evidence that IL-4 and I L-13 share receptor components, including IL-4R alpha and IL-13R alpha 1 [9]. In order to dissect the roles of IL-4 and IL-13 in the regulat ion of Th2 cells and in the response to nematode infections, we looked for differences between mice deficient for either the IL-4 gene or th e IL-4R alpha gene. Unlike IL-4, IL-4R alpha was required for control of N. brasiliensis, and Th2 development during infection - as characte rized by cytokine production, GATA-3 and surface CD30 expression - was more severely affected in IL-4R alpha(-/-) mice than in IL-4(-/-) mic e, Injection of recombinant IL-13 induced worm expulsion in otherwise incompetent RAG2(-/-) mice. Our results suggest that IL-13 regulates T h2 responses to nematode infection and requires IL-4R alpha. (C) Curre nt Biology Ltd ISSN 0960-9822.