The long range goal of these studies is to provide a detailed understanding of the mechanism by which macrophages process and present antigen to lymphocytes. In this regard, attempts will be made to understand the interactions of macrophages with the facultative intracellular pathogen Listeria monocyogenes. Assays for macrophage-dependent T lymphocyte activation in vitro will be used. Antigenic determinants associated with the bacteria and expressed by macrophages infected with the bacteria will be detected with monoclonal antibodies and T cell lines and hybridomas. Detailed study of the antigenic structures of L monocytogenes will be performed using such tools in combination with molecular genetic techniques. The molecular and cellular mechanisms underlying the differential requirements for antigen processing requirements with different forms of listerial antigens will be studied. Experiments will be performed to evaluate the effects of the fungal polypeptide, cyclosporine, on macrophage-dependent in the facilitation of clinical organ transplantation, its precise mode of action remains unknown. Future experiments will be performed to clarify the mechanism of the apparent inhibition of antigen presentation function by cyclosporine. These studies should further the understanding of the mechanisms by which intracellular pathogens Listeria and fungal products (cyclosporine) regulate macrophage and lymphocyte function and how immunity to microorganisms is generated and expressed.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI020215-08
Application #
3129735
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Project Start
1983-08-01
Project End
1992-08-31
Budget Start
1990-09-01
Budget End
1992-08-31
Support Year
8
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Emory University
Department
Type
Schools of Medicine
DUNS #
042250712
City
Atlanta
State
GA
Country
United States
Zip Code
30322
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Safley, S A; Jensen, P E; Reay, P A et al. (1995) Mechanisms of T cell epitope immunodominance analyzed in murine listeriosis. J Immunol 155:4355-66
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Verma, N K; Ziegler, H K; Wilson, M et al. (1995) Delivery of class I and class II MHC-restricted T-cell epitopes of listeriolysin of Listeria monocytogenes by attenuated Salmonella. Vaccine 13:142-50
Skeen, M J; Ziegler, H K (1993) Induction of murine peritoneal gamma/delta T cells and their role in resistance to bacterial infection. J Exp Med 178:971-84
Skeen, M J; Ziegler, H K (1993) Intercellular interactions and cytokine responsiveness of peritoneal alpha/beta and gamma/delta T cells from Listeria-infected mice: synergistic effects of interleukin 1 and 7 on gamma/delta T cells. J Exp Med 178:985-96

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