Despite their critical role in certain immune responses, a clear understanding of the mechanisms by which cytotoxic T lymphocytes (CTL) bring about their effector function is presently lacking. The identification of each of the gene products that compose the cytolytic apparatus of these cells is clearly a prerequisite for a full understanding of this effector response. Thus, the overall goal of this project is to identify gene products involved in CTL-mediated lysis and to determine their roles in the cytolytic process. Progress has recently been made toward this goal by isolating and characterizing two novel CTL-specific genes; a cytokine-inducible molecule with lipase activity and the calcium-binding protein casein. This proposal reflects both molecular and genetic approaches toward expanding these initial observations. In particular, we wish to 1) elucidate the role of CTL lipase and casein in CTL function; 2) generate loss of function mutants of CTL-specific genes in CTL clones and transgenic animals using homologous recombination techniques, and 3) isolate and characterize additional cytokine-inducible and CTL-specific genes. This information will be invaluable both in understanding the role of CTL in various disease processes, and in the design of potential therapies for various autoimmune diseases in which CTL have been implicated.
| Lowe, M E; Kaplan, M H; Jackson-Grusby, L et al. (1998) Decreased neonatal dietary fat absorption and T cell cytotoxicity in pancreatic lipase-related protein 2-deficient mice. J Biol Chem 273:31215-21 |
| Smiley, S T; Grusby, M J (1997) Dual-receptor T cells expressing one self-restricted TCR. Scand J Immunol 45:726-30 |
| Smiley, S T; Stitt, T N; Grusby, M J (1997) Cross-linking of protein S bound to lymphocytes promotes aggregation and inhibits proliferation. Cell Immunol 181:120-6 |
| Smiley, S T; Boyer, S N; Heeb, M J et al. (1997) Protein S is inducible by interleukin 4 in T cells and inhibits lymphoid cell procoagulant activity. Proc Natl Acad Sci U S A 94:11484-9 |
| Kaplan, M H; Boyer, S N; Grusby, M J (1996) Genomic organization of the murine CTL lipase gene. Genomics 35:606-9 |
