The immune system is remarkable in its ability to mount responses against a wide array of antigens and to respond with enhanced vigor to antigens encountered in the past. This exaggerated recall immune response, or immune memory, is a central concept in immunology. It forms the basis of vaccination against infectious diseases. Immune memory is mediated by memory lymphocytes that persist in the host long after resolution of the infection or antigenic insult. The long-range goal of our lab is to understand how immune memory is generated, regulated, and maintained. To study immune memory, we have generated a novel and powerful transgenic mouse model system. In this system, both effector and memory pools of T lymphocytes are indelibly tagged with the marker _ galactosidase by an irreversible cre-lox recombination event. This allows us to map the fate of activated CD8 T cells in vivo. We use this model system to probe lymphocytic choriomeningitis (LCMV) virus-induced immune responses and the differentiation pathway of immune memory generation. We have also initiated studies aimed at understanding the role of DNA methylation in generation and maintenance of effector and memory CD8 T cells by selectively ablating the DNA methyltransferase, Dnmt-1 in these cells.

Recently, we have also developed a novel strategy to mark and track dendritic cells (DC). DCs are highly potent antigen-presenting cells and the functions as key regulators of immune responses. They initiate antigen-specific immune responses by acquiring antigens in peripheral tissues, migrating to lymphoid organs, and presenting these antigens as processed peptides to T cells. Despite its critical role, the persistence, phenotype, and clonal dynamics of antigen-bearing DCs involved in initiating an immune response remains unclear. We have used cre-lox recombination to permanently mark antigen-bearing dendritic cells at the site of immunization (abdominal epidermis) and track them in the draining lymph nodes. Interestingly, following gene gun immunization, we found that the number of antigen-bearing dendritic cells in the draining lymph node is one hundred times higher than previous estimates.

[joshy.jacob@microbio.emory.edu]

WEBSITE: [http://www.microbiology.emory.edu/jacob/]