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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
7R01AI024355-01
Application #
3137356
Study Section
Tropical Medicine and Parasitology Study Section (TMP)
Project Start
1986-07-01
Project End
1987-06-30
Budget Start
1986-07-01
Budget End
1987-06-30
Support Year
1
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Type
Schools of Veterinary Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
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