A T cell subpopulation present in alloimmune mouse spleens (but not in normal spleens) kills target cells non-specifically in the presence of lectins (e.g. Con A), but not in their absence. Fractionation of immune spleen cells on allogeneic monolayers showed that the Con A dependent killer cell was not the classical, directly cytotoxic, effector T cell (the latter cell bound specifically to homologous allogeneic monolayers, the Con A-dependent T cell did not). We wish to explore the hypothesis that the Con A-dependent killer cell is a precursor of the directly cytotoxic T cell. To show this we will attempt to generate Con A-dependent killer cells in vitro with alloantigen and to assay when this population arises relative to T effector and T memory populations. Additionally, we will define whether Con A-dependent killer cells are: a) exclusively induced by alloantigenic immunization and b) to explore the spectrum of target cells which they can kill in the presence of lectin. The relationship between the Con A-dependent killer cells and memory cell populations will be explored by studying the effects on these two populations of repeated exposure to antigen in vitro. A second, major, emphasis of this study is addressed at comparing the mechanism of action of Con A-dependent killer cells with directly cytotoxic T cells and with K cells (those effectors capable of lysing antibody coated target cells). This address will center on the ability of different effector cells to cause membrane permeability changes across haptenated synthetic bimolecular lipid membranes ("black" membranes) and across uni- and multivesicular liposomes. The composition of the bimolecular lipid membranes will be systematically altered and the effects on cell-mediated ion permeability changes compared with those effects caused by antibody in the presence of guinea pig complement. These studies are aimed at implicating the phospholipid bilayer of the plasma membrane as a common substrate for lymphocyte attack.
NIH ExPorter
NIH ExPorter