Migration Properties of Naive, Effector, and Memory T cells

The recruitment of T cells to lymphoid organs and peripheral tissues is a central aspect of an immune response to microorganisms, vaccines or tumors. T cell migration is a strictly-regulated multistep process that is highly tissue- specific and is mediated by the differential expression of adhesion molecules and chemokine receptors. Although a great deal has been learned regarding native T cell recirculation through secondary lymphoid organs, several aspects of antigen-primed T cell migration remain unresolved. In the current proposal we will analyze (1) why native T cells are excluded from peripheral sites of inflammation using a novel mouse strain, called T-GFP, in which all native T cells express the green fluoresent protein. Aim (2) will make use of a newly-developed in vitro system which generates large numbers of antigen-specific effector and central memory CD8+ T cells. The in vivo migration behavior of these cells will be compared using homing assays and intravital microscopy. In aim (3) we will develop in vitro conditions that allow for generation of effector and central memory CD4+ T cells. Many aspects of this proposal are completely novel, including the use of the T-GFP mouse strain, the generation of memory cells, as well as intravital microscopy of peripheral lymph nodes. These state-of-the-art techniques are currently not performed in any other laboratory, therefore this provides a unique opportunity for the applicant to acquire specialised knowledge currently unavailable elsewhere in the world. Some of the answers to the questions raised should greatly enhance our understanding of T cell traffic and hence, our understanding of tumor and infection immunology as well as vaccine development.