IMMUNOGENETICS OF TRICHINELLA SPIRALIS INTHE MOUSE

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Two H-2 genes, Ts-1 and Ts-2, are known to influence the immune response against T. spiralis in the mouse. Evidence suggests that T-T cell interaction is required to generate an efficient immune response, and that susceptible mice express a Ts-2 associated defect in one of the interacting T cell populations. Immunogenetic experiments in genetically characterized H-2 congenic strains of mice will establish whether or not T-T cell interaction is required for an efficient response, characterize the cells involved, and identify the cell population expressing the Ts-2-associated defect. To accomplish these aims, selected populations of lymph node cells will be injected into genetically characterized, T cell deficient or normal mice. These mice will then be infected with T. spiralis and their levels of resistance measured. T cell deficient recipients of cells will be thymectomized, irradiated, and reconstituted with syngeneic bone marrow. T. spiralis-educated T cells used for transfer will be from irradiated, thymocyte reconstituted mice or from normal mice infected with T. spiralis. T. spiralis-educated cells will be injected into recipients either alone or in combination with selected cell populations from normal mice. Monoclonal antibody specific for the Thy-1 and Ly antigens expressed on T cells and for the Ia antigens expressed on B cells, macrophages and subpopulations of T cells will be used to carefully define the composition of cells being transferred. Results of these in vivo experiments will be confirmed by studying the cell-cell interactions required to generate a maximal in vitro proliferation response to highly purified, protection inducing T. spiralis antigens. To complement the above studies and to further explore the role of T cells and antibody in effecting the immune response against T. spiralis, we will test the in vivo effect of injecting mice with cloned T cells and with monoclonal antibody specific for protection inducing antigens of T. spiralis. The role of parasite-induced immunosuppression will likewise be explored by injecting mice with preparations of T. spiralis-specific I-J+ suppressor factors secreted by suppressor T cell hybridomas. Monoclonal antibody, T cell clones and suppressor factors will also be used to purify and characterize relevant T. spiralis antigens.