Human IgE production in hu-PBL-SCID mice injected with birch pollen and diesel exhaust particles.

Mice with severe combined immunodeficiency were transplanted with human peripheral blood lymphocytes (hu-PBL-SCID mice). The response to immunisation with birch pollen was used to study possible effects of diesel exhaust particles (DEP) and aluminium hydroxide (Al(OH)3) on human IgE production in this human in vivo model. The adjuvants were well tolerated, as determined by the number of human cells in the peritoneal cavity at the end of the experiments. Total and birch pollen-specific IgE was detected in 76 and 41% of the mice, respectively. In the present experiments where the mice were stimulated early with birch pollen, a doubling in percentage of hu-PBL-SCID mice with production of specific IgE was observed, as compared to later stimulation used in previous experiments. Although a tendency to higher total IgE levels was observed after treatment with DEP, no statistically significant adjuvant effect of DEP or Al(OH)3 could be demonstrated. Electron microscopy analysis after immunogold labelling showed that the major birch pollen allergen Bet v I was released from the pollen grains and adsorbed to the surface of the DEP. Early stimulation with allergen appears to be important for optimal production of specific IgE in the hu-PBL-SCID model. However, our results show that further improvements are needed in order to demonstrate the expected effects from adjuvants and environmental pollutants.

Total and birch pollen-specific human IgE in mice with severe combined immunodeficiency transplanted with human peripheral blood lymphocytes: donor dependence, seasonal variation and in vivo half-life.

BACKGROUND: There is a need for animal in vivo models in the study of human allergy. The aim of the present experiments was to study production and catabolism of human IgE in mice with severe combined immunodeficiency transplanted with human peripheral blood lymphocytes (hu-PBL-SCID mice). METHODS: Groups of SCID mice were transplanted intraperitoneally with hu-PBL from the same three donors in five experiments. Subgroups of transplanted mice were immunized with birch pollen. Production of human total and birch pollen-specific IgE in the hu-PBL-SCID mice was analyzed over a 7-week period. RESULTS: Human IgE was detected in 93% of the hu-PBL-SCID mice, and the production showed reproducible donor-dependent kinetics. Production of birch pollen-specific human IgE, however, was seen only in mice transplanted with cells from birch pollen-allergic donors. A greater proportion of the mice produced specific IgE when the experiment was started in, or some months after a birch pollen season with high pollen counts. The half-lives of passively transferred human IgE were determined to be 24.0 and 23.4 h for total and birch pollen-specific IgE, respectively. CONCLUSIONS: This study demonstrates that human IgE production in hu-PBL-SCID mice is very reproducible when the same donor is used several times. Specific IgE production in recipient mice seems to require the use of cell donors with the actual specific allergy, and is most readily obtained during or after a period of donor allergen exposure. The short half-lives found indicate that hu-PBL-SCID mice have a high ongoing production of human IgE.