AN IN-VIVO MODEL OF ALLERGIC INFLAMMATION - PULMONARY HUMAN CELL INFILTRATE IN ALLERGEN-CHALLENGED ALLERGIC HU-SCID MICE

CB.17 severe combined immunodeficient (SCID) mice were used to establi sh a model of allergic pulmonary inflammation. SCID mice were intraper itoneally reconstituted with 10(7) peripheral blood mononuclear cells (PBMC) from patients sensitive to Dermatophagoides pteronyssinus (Dpt) and 2 weeks later were exposed to Dpt aerosols. After Dpt nebulizatio n, SCID mice engrafted with PBMC from Dpt-sensitive patients developed a specific human ISE response as well as an intense pulmonary infiltr ate of human cells. In contrast, SCID mice reconstituted with PBMC fro m patients allergic to grass pollen or from non-allegic donors failed to produce IgE or to exhibit a similar inflammatory response. The leve l of the IgE production was dependent on the IgE level of the allergic donor In the lungs of the same allergic SCID mice, 2 months after Dpt inhalation, the cell infiltrate contained CD45(+), CD45RO(-), CD20(+) and HLA-DR(+) human cells. They were located in perivascular and peri bronchial areas and disseminated in the mouse lung parenchyma. Moreove r mRNA IL-5(+) cells and eosinophils were found in peribronchial infil trates. The observations indicate that humanized allergic SCID mice ma y develop, after nebulization with the relevant allergen, immune react ions similar to those observed in man and suggest that SCID mice may r epresent a useful model to analyze the regulatory mechanisms of IgE-as sociated allergic diseases.