Mice are extensively used to study the development of allergic immune responses. Over the last years we have de veloped an animal model to study the allergic immune re sponse under in vivo conditions. It was shown that local and systemic sensitization of susceptible mice (such als BALB/C or C57/BL6) resulted in the formation of allergenspecific IgE antibodies that could be detected in the serum by ELISA [1]. This immune response is of functional rele vance since mice producing allergen-specific IgE or IgGl antibodies develop positive immediate-type skin test re sponses following local allergen challenge on the skin [2], Furthermore, when those mice were challenged with the al lergen via the airways and the lung, a state of increased air way responsiveness was measured using in vivo and in vitro techniques for the assessment of long functions [3]. These types of response were found to be dependent on CD4+ and CD8+ lymphocyte subsets that produce pro-allergic cyto kines including 1L-4 and IL-5 [4]. Although such animal models have several advantages to delineate the development of allergic immune responses, there always is a question of relevance of such findings for allergic immune responses in man. On the other hand, there are many reasons and aspects that limit the opportunity to study local immunological dysregulations in patients. For these and other reasons, we set out to develop an animal model that would allow one to study the human immune system under in vivo conditions.

Transfer of peripheral blood mononuclear cells (PBMC) from allergic patients characterized by elevated total and al lergen specific IgE antibody titers into SCID mice resulted in the production of total and allergen specific human IgE in these animals. This type of immune response was depend ent on several factors: Hu-lgE antibody titers could only be detected in those SCID mice that were repopulated with cells from allergic patients, but not when cells from normal nonsensitized nonallergic individuals were used for the cell transfer. Another prerequisite was the simultaneous expo sure to the clinically relevant allergen. In our study, we se lected house dust mite allergen (Der p) as a model allergen of great clinical relevance. Even in patients that exhibited high allergen-specific IgE antibody titers, an allergen boost was required in order to induce allergen-specific Hu-lgE antibodies in reconstituted SCID mice. These results point to several important aspects in terms of the immuno-regulation of Hu-lgE antibody production: the atopic immune system shows significant differences compared to nonatopic individuals. These differences may include composition of T cell subsets, preactivation of T cells in allergic individuals and the presence of already IgE committed B cells in atopic patients. However, although a large number of IgE-committed B cells was present in the transferred PBMC population, additional allergen challeng es were required in order to promote the production of al lergen-specific IgE. These data indicate that even IgE-com mitted B-cells require the continuous exposure to the aller gen in order to produce IgE antibodies. On the other hand, if allergen exposure was avoided, there was no allergen-spe-