A few studies in rodents and humans have identified immunologic cells that possess both lytic and antigen presenting function. We have found cells expressing both the natural killer (NK) cell marker NK1.1 as well as the dendritic cell (DC) marker CD11c, in multiple organs of normal mice. We have established that these natural killer dendritic cells (NKDC) can lyse tumor cells, present tumor-derived antigen, and activate na?ve T cells in vitro. In addition, we have discovered that activated NKDC secrete high levels of IFN-gamma. Overall, though, very little is known about NKDC. With this proposal, we will establish the scientific foundation to understand NKDC biology.
In Aim 1, we will delineate the regulation of IFN-gamma production by NKDC. In addition, we will test how activation and Flt3 ligand-mediated expansion each affect NKDC phenotype and function.
In Aim 2, we will use NKDC to prevent or treat tumors in mice. The contribution of T cell stimulation, NKDC lytic function, and NKDC IFN-gamma production to the anti-tumor activity of NKDC will be investigated. We anticipate that our findings will elucidate how this novel cell type may contribute to a variety of immune processes and how NKDC may be useful in the treatment of cancer. ? ? ? ?
| Burt, Bryan M; Plitas, George; Zhao, Zeguo et al. (2009) The lytic potential of human liver NK cells is restricted by their limited expression of inhibitory killer Ig-like receptors. J Immunol 183:1789-96 |
| Burt, Bryan M; Plitas, George; Nguyen, Hoang M et al. (2008) Circulating HLA-DR(+) natural killer cells have potent lytic ability and weak antigen-presenting cell function. Hum Immunol 69:469-74 |
| Burt, Bryan M; Plitas, George; Stableford, Jennifer A et al. (2008) CD11c identifies a subset of murine liver natural killer cells that responds to adenoviral hepatitis. J Leukoc Biol 84:1039-46 |
