Development and functional studies of human dendritic cell populations
We propose that the human DC system has basic similarities with the mouse DC system and contains several phenotypically and functionally discrete subsets. This study will directly translate the knowledge obtained from studies of mouse DC biology into human DC studies and allow us to progress beyond the analysis of human blood alone. We have recently established a Flt3L culture system for generating steady state DC subsets from mouse bone marrow precursors. Functional analysis of these DC subsets generated in culture confirmed that they represent the equivalents of the steady state DC subsets identified in mouse spleen. In this study, we aim to establish a similar in vitro system that can support the development of steady state DC populations from human hemopoietic progenitors. We will also compare the phenotype and functions of DC populations generated in culture with those isolated from human lymphoid tissues. A clear understanding of the functional differences of human DC subsets is essential in selecting appropriate DC subtypes for developing effective vaccines or immuno-therapies.