Hyper immunoglobulin E response in mice with monoclonal populations of B and T lymphocytes

A key event in the pathogenesis of allergies is the production of antibodie s of the immunoglobulin (Ig)E class. In normal individuals the levels of Ig E are tightly regulated, as illustrated by the low serum IgE concentration. In addition, multiple immunizations are usually required to generate detec table IgE responses in normal experimental animals. To define the parameter s that regulate IgE production in vivo, we generated mice bearing monoclona l populations of B and T lymphocytes specific for influenza virus hemagglut inin (HA) and chicken ovalbumin (OVA), respectively. A single immunization of the monoclonal mice with the cross-linked OVA-HA antigen led to serum Ig E levels that reached 30-200 mug/ml. This unusually high IgE response was p revented by the infusion of regulatory alpha/beta CD4(+) T cells belonging to both CD25(+) and CD25(-) subpopulations. The regulation by the infused T cells impeded the development of fully competent OVA-specific effector/mem ory Th2 lymphocytes without inhibiting the initial proliferative response o f T cells or promoting activation-induced cell death. Our results indicate that hyper IgE responses do not occur in normal individuals due to the pres ence of regulatory T cells, and imply that the induction of regulatory CD4( +) T cells could be used for the prevention of atopy.