Lipopolysaccharide stimulation converts vigorously washed dendritic cells (DCs) to nonexhausted DCs expressing CD70 and evoking long-lasting type 1 T cell responses

A great variety of in vitro culture pro- tocols for human monocyte-derived dendritic cells (mo-DCs) has been used to generate DCs suitable for use in immunotherapy. It is thought that acti- vated DCs undergo one-way differentiation into "exhausted" DCs. In the present study, we con- trived an in vitro method for facilitating expression of CD70 by mature DCs. This was achieved by vigorous washing of mo-DCs before exposure to lipopolysaccharide (LPS). Unexpectedly, these ma- ture DCs retain expression of some interleukin (IL)-12 family members after extended periods and maintain their ability to stimulate type 1 T cell responses. In contrast, DCs exposed to IL-4 before LPS stimulation or LPS-stimulated DCs not ex- posed to washing stress before activation failed to express CD70 and did differentiate into exhausted DCs. It is interesting that DCs expressing CD70 (CD70 DCs) induced interferon- production from purified, allogeneic CD8 T cells through a direct CD27-CD70 interaction. This is evidence for a pathway resulting in generation of CD8 T effectors by B7-independent mechanisms. These data suggest that exposure of immature DCs to LPS stimulation contributes to their terminal differen- tiation into CD70 DCs, which have potent ability to prolong type 1 T cell responses through alter- native pathways. J. Leukoc. Biol. 78: 000-000; 2005.