A colony of inbred """"""""atopic"""""""" dogs has been developed in the past 3 years. These dogs make large amounts of IGE specific antibodies to pollens, have positive skin tests, and evidence bronchospasm upon inhalation of the pollens. The colony currently consists of 20 animals including 12 third generation breeders, 4 sibling sires and 4 younger litter members.
Our specific aims i n this renewal proposal are: 1) to continue development of this inbred colony and, 3) to firmly establish the reproducibility of the """"""""asthmatic"""""""" criteria of these animals' bronchial responsiveness to pollen antigens and non-specific stimuli, such as methacholine and histamine. Our second specific aim is to study the effects of experimentally induced virus infections upon IgE antibody production and bronchial responsiveness in these animals. This model was developed by first selecting and breeding high pollen skin reactive hunting breeds. Their young puppies were given live virus vaccines concomitant with immunization with ragweed and grass pollen extracts. Larger amounts of IgE antibodies to the pollens developed in the vaccinated animals than in littermate controls. We plan to study 6 litters from the colony with single doses of distemper vaccine and pollen at either 1, 2 or 3 months of age to determine the minimal exposure and optimal age required for allergic sensitization. Littermate controls will receive either vaccine or pollen or neither. Pups will be tested, subsequently, for IgE antibodies and bronchoreactivity to pollens and nonspecific stimuli. Preliminary studies indicate that these dogs' airways are hyperreactive to both; therefore, they closely resemble human asthmatics. Pups will also be exposed to a canine parainfluenza-infected nursing mother to infect the pups with a natural virus infection and concomitantly expose them to pollen aerosol inhalations to simulate a natural exposure to these agents. Finally, 4) we plan to study virus effects on immunomodulation of IgE antibody production by following serially, changes in T-helper and T-suppressor cells induced by virus infections in pups. For this, we plan to develop rabbit polyclonal and mouse monoclonal antibodies against canine T-lymphocyte subsets. In future studies, immunologic and pharmacologic manipulations of immunomodulatory cells might prevent allergy sensitization in pups. Such measures could then applied for prevention of allergy in atopy-prone children.
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