Cellular events underlying the expression of resistance to Listeria monocytogenes (LM) would be analyzed in a model system using rats. Central to the proposed inquiry is the relationship between delayed type hypersensitivity (DTH) and acquired cellular resistance to infection (CRI). These two phenomena are mediated by T cells which have distinctive phenotypic characteristics, gene constraints, and possibly different lymphokine repertoires. But the two major subsets to which TDTH and TCRI belong are themselves heterogeneous. Each contain cells that have distinctive surface antigenic profiles and functional properties. A major objective of the proposed investigation is to systematically define these subsets and to ascertain the capacity of their component cells to interact with one another and with macrophages. To that end monoclonal antibodies, panning techniques and both new and established methods of flow cytometry would be used to isolate T cell subsets from the central lymph of LM infected rats. Using sensitive and reproducible assays we would ascertain the effective life span of the cells, their tissue disposition in recipient rats, gene restriction, and capacity to influence the local deployment of T cells and macrophages in DTH reaction sites and centers of infection. The above findings would be correlated with the lymphokine repertoire of subset defined T cells and their capacity to influence the microbicidal activity of macrophages. Subsidiary questions to be addressed include the role of suppressor T cells (Ts) in regulating the production of TDTH and TCRI; whether the sensitivity elicited by living LM involves the activity of additional or possibly different TDTH from those engaged by soluble Listeria antigens or killed bacteria; and whether relevant T cell subsets can be engaged selectively by altering the immunization strategy in various ways. Still another aspect of the proposed investigation would focus on a critical early event in the delayed inflammatory reaction. We wish to test the proposition that fibronectin (FN) functions as a ligand between recently activated T cells and inflamed vascular endothelium; the type(s) of FN and T cells involved, and whether that interaction can be modified in useful ways.
| Chen-Woan, M; McGregor, D D; Noonan, S K (1986) Isolation and characterization of protective T cells induced by Listeria monocytogenes. Infect Immun 52:401-7 |
| Chen-Woan, M; McGregor, D D; Harris, W V et al. (1986) Monoclonal antibody analysis of Listeria monocytogenes-induced cytotoxic lymphocytes. Immunology 57:505-13 |
| Chen-Woan, M; Sajewski, D H; McGregor, D D (1985) T-cell co-operation in the mediation of acquired resistance to Listeria monocytogenes. Immunology 56:33-42 |
