IMMUNE-RESPONSES OF IL-5 TRANSGENIC MICE TO PARASITES AND AEROALLERGENS

Eosinophils have long been thought to be effectors of immunity to helm inths but have also been implicated in the pathogenesis of asthma. Pat terns of cytokine production in the host may influence the pathogenesi s of these diseases by regulating the activities of eosinophils and ot her components of the immune response. Mice which constitutively over- express IL-5 have profound and life-long eosinophilia in a restricted number of tissues. Although eosinophils from IL-5 transgenics are func tionally competent for a number of parameters considered to be importa nt in inflammation, untreated animals are overtly normal and free of d isease. In addition, the responses of these animals when exposed to ae roallergens and helminths present a number of apparent paradoxes. Eosi nophil accumulation in tissues adjacent to major-airways is rapid and extensive in transgenics exposed to the aeroallergen, but even after t reatment with antigen over many months these mice show no evidence of respiratory distress or pathology. Helminth-infected IL-5 transgenics and their non-transgenic littermates develop similar inflammatory resp onses at mucosal sites and are comparable for a number-of T cell and a ntibody responses, but they differ considerably in their ability to cl ear some parasite species. The life-cycle of Nippostrongylus brasilien sis is significantly inhibited in IL-5 transgenics, but that of Toxoca ra canis is not. Our results also suggest that eosinophilia and/or ove r-expression of IL-5 may actually impair host resistance to Schistosom a mansoni and Trichinella spiralis. The pathogenesis of diseases in wh ich eosinophils are involved may therefore be more complex than previo usly thought.