Dendritic cells induce peripheral T cell unresponsiveness under steady state conditions in vivo

Dendritic cells (DCs) have the capacity to initiate immune responses, but i t has been postulated that they may also be involved in inducing peripheral tolerance. To examine the function of DCs in the steady state we devised a n antigen delivery system targeting these specialized antigen presenting ce lls in vivo using a monoclonal antibody to a DC-restricted endocytic recept or, DEC-205. Our experiments show that this route of antigen delivery to DC s is several orders of magnitude more efficient than free peptide in comple te Freund's adjuvant (CFA) in inducing T cell activation and cell division. However, T cells activated by antigen delivered to DCs are not polarized t o produce T helper type 1 cytokine interferon gamma and the activation resp onse is not sustained. Within 7 d the number of antigen-specific T cells is severely reduced, and the residual T cells become unresponsive to systemic challenge with antigen in CFA. Coinjection of the DC-targeted antigen and anti-CD40 agonistic antibody changes the outcome from tolerance to prolonge d T cell activation and immunity. We conclude that in the absence of additi onal stimuli DCs induce transient antigen-specific T cell activation follow ed by T cell deletion and unresponsiveness.