Tolerance induction to self antigens by peripheral dendritic cells.

It has been suggested, but not formally demonstrated, that peripheral dendritic cells (DC) alone are capable of tolerance induction by clonal deletion and/or anergy. To resolve such an issue, it is important to develop in vivo systems where DC are the only cells capable of presenting antigen and where a T cell population with a known antigen specificity can be followed. Here we use a transgenic murine model, which expresses the influenza virus hemagglutinin (HA) on B cells and on CD8alpha(+) and CD8alpha(-) DC but not on macrophages. If these mice are on a RAG(-/-) background, one has a model in which only DC present the HA antigen. In these mice, HA-specific T cells are deleted very efficiently in the thymus and those remaining in the periphery cannot respond to further antigenic stimulation in vitro and cannot eliminate antigen in vivo. By performing adoptive transfers, we show for the first time that self-antigen presentation exclusively by peripheral DC results in very efficient clonal deletion of the majority of antigen-specific T cells with the remaining ones in an anergic state. This model will permit us to further address the mechanisms by which DC tolerize or prime T cells and to investigate whether anergy induction by DC is similar to anergy induction by B cells.