Granulomatous disease, a major cause of pulmonary dysfunction, is an integral component of visceral larva migrans (VLM) syndrome due to infection with Toxocara canis. Seroepidemiological findings indicate that in parts of the United States, 20 to 30% of the pediatric population may be infected with T. canis. Little is known about host immunity to this nematode. Previous studies have been carried out to dissect the role of splenic T lymphocytes in the regulation of Toxocara- specific pulmonary granuloma formation with no success. All attempts to transfer granulomatous hypersensitivity from infected mice to naive recipients using spleen cells or hyperimmune serum from infected mice have failed. Recent studies suggest that less than 5% of the T cells in the spleens of T. canis-infected mice are antigen specific whereas between 20 and 95% of the T cells in the lung are. By transferring inflammatory cells obtained by bronchoalveolar lavage of mice infected with T. canis directly into the lungs of naive recipients, granulomatous hypersensitivity can be successfully transferred. Therefore, we now have a model system in which we can study the immunoregulation of the pulmonary inflammatory reaction in mice infected with Toxocara and by embolizing antigen-coated beads into the lung, we can study granuloma formation in the absence of systemic sensitization. This proposal seeks to continue the studies carried out in the original proposal. It will extend them by characterizing the T lymphocytes in the pulmonary infiltrate of the lungs of infected mice and compare them with the T cells in the spleen especially as regards their role in the induction and elicitation of artificial pulmonary granulomas that form around sepharose beads covalently coated with Toxocara exoantigens (TEX).
The aims of this proposal are to 1) compare the immunologic properties of the pulmonary infiltrate lymphocytes, found in the local environment of granuloma formation in Toxocara-infected mice, with splenic lymphocytes; 2) determine the role of T lymphocytes, including helper and effector subsets, in the formation of the TEX-coated bead granuloma in Toxocara-infected mice; 3) evaluate lymphokine production of the kinds deemed essestial for eosinophilrich granuloma formation by cells of the pulmony infiltrate relative to spleen cells in mice infected with Toxocara; and 4) define the relationship between the number of different T cell types in the pulmonary infiltrate and larval worm burden with respect to length of infection in mice infected with Toxocara. In the short term, these studies will allow an insight into specific organ immunity as compared with the usually studies systemic immunity of the spleen. The long-range goal of these studies is to understand the interactions of the cells comprising the inflammatory infiltrate.
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