IN-VIVO MIGRATION OF DENDRITIC CELLS DIFFERENTIATED IN-VITRO - A CHIMPANZEE MODEL

Dendritic cells with potent Ag-presenting function can be propagated f rom peripheral blood using recombinant cytokines, and these cells have potential usefulness as immunotherapeutic agents in the treatment of cancer and other disease states, However, it is not known if these in vitro differentiated dendritic cells have the capacity to migrate in v ivo, especially to T cell areas of lymphoid tissue. We have used a flu orescent marker system to track the migration of dendritic cells, prop agated in vitro from chimpanzee peripheral blood, following s.c. injec tion. We report that injected dendritic cells migrate spontaneously an d rapidly to draining lymph nodes, where they remain for at least 5 da ys. The injected cells interdigitate with T cells in the parafollicula r and paracortical zones and retain high level expression of CD86, CD4 0, and MHC class II molecules, reflecting a phenotype of potent APC. W e conclude that dendritic cells differentiated in vitro from periphera l blood and administered s.c. behave in a manner very similar to endog enous Langerhans cells. These data provide strong experimental support , in a highly relevant large animal model, for the use of in vitro dif ferentiated dendritic cells as vehicles for immunotherapy, More import antly, they show that the s.c. route of injection delivers these APC t o sites of T cell activation, a prerequisite for the generation of an effective immune response.