Listeria monocytogenes is a hemolysin producing bacterium that can survive and multiply within various cells of the body. This microbe causes disease in the very young, the elderly and the immunocompromised. The development of immunity to Listeria as well as many other intracellular parasites involves cooperation between T cell subsets as well as between T cell subsets and macrophages. In the murine model, we have recently established that the L3T4-, Ly2+ T cell subset provides the effector lymphocyte function requires for immunity to L monocytogenes. We have also determined that the effector function of this population as expressed in vivo can be considerably enhanced and the duration of its expression dramatically prolonged by an in vitro culture period prior to cell transfer. The significant increase in adoptively transferred immunity is found exclusively within the cell population possessing the L3T4-, Ly2+ phenotype, a surface marker also associated with cytotoxic cells. (Cytotoxic activity has recently been shown to exist against Listeria-infected targets but its relevance has not been determined for this facultative parasite). The focus of our proposed studies is on the culture-activated effector cell and is divided into three areas of analysis. Firstly, we will correlate the in vivo protective function of the effector cell with its cytotoxicity and will determine the MHC regulation of these in vivo and in vitro activities. These studies will use cells, activated by the culture environment, to transfer immunity to congenic mice which differ from the donor in defined regions of the MHC. The influence of this MHC difference will also be evaluated by the cytotoxicity of the cells from culture using Listeria-infected macrophages as the cytotoxic cell target. Secondly, we will evaluate the in vitro requirements which provide the necessary conditions for the development of the long-lived effector cell. This set of experiments will attempt to determine the precursor cell as well as the signals and T cell subset cooperation required for the in vitro development of the long-lived effector cell. Finally, we will use the Listeria-specific cytotoxic cell to evaluate the processing events that allow the development of the cytotoxic cell target. These studies will establish if antigen association with Class I and Class II MHC encoded surface molecules is dependent on the physical state of the antigen encountered by the cells. Additionally, cytotoxic target development will be studied with cells that express Class I and Class II surface molecules (macrophages) and will be compared with cells that only express Class I surface molecules (fibroblasts).
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