PMID- 11560993 OWN - NLM STAT- MEDLINE DCOM- 20011025 LR - 20240213 IS - 0022-1007 (Print) IS - 1540-9538 (Electronic) IS - 0022-1007 (Linking) VI - 194 IP - 6 DP - 2001 Sep 17 TI - Dendritic cells induce peripheral T cell unresponsiveness under steady state conditions in vivo. PG - 769-79 AB - Dendritic cells (DCs) have the capacity to initiate immune responses, but it 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 an antigen delivery system targeting these specialized antigen presenting cells in vivo using a monoclonal antibody to a DC-restricted endocytic receptor, DEC-205. Our experiments show that this route of antigen delivery to DCs is several orders of magnitude more efficient than free peptide in complete Freund's adjuvant (CFA) in inducing T cell activation and cell division. However, T cells activated by antigen delivered to DCs are not polarized to produce T helper type 1 cytokine interferon gamma and the activation response 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 prolonged T cell activation and immunity. We conclude that in the absence of additional stimuli DCs induce transient antigen-specific T cell activation followed by T cell deletion and unresponsiveness. FAU - Hawiger, D AU - Hawiger D AD - Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10021, USA. FAU - Inaba, K AU - Inaba K FAU - Dorsett, Y AU - Dorsett Y FAU - Guo, M AU - Guo M FAU - Mahnke, K AU - Mahnke K FAU - Rivera, M AU - Rivera M FAU - Ravetch, J V AU - Ravetch JV FAU - Steinman, R M AU - Steinman RM FAU - Nussenzweig, M C AU - Nussenzweig MC LA - eng GR - R01 AI013013/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Exp Med JT - The Journal of experimental medicine JID - 2985109R RN - 0 (Antigens, CD) RN - 0 (B7-2 Antigen) RN - 0 (CD40 Antigens) RN - 0 (Cd86 protein, mouse) RN - 0 (DEC-205 receptor) RN - 0 (Lectins, C-Type) RN - 0 (Membrane Glycoproteins) RN - 0 (Minor Histocompatibility Antigens) RN - 0 (Receptors, Cell Surface) RN - EC 3.2.1.- (hen egg lysozyme) RN - EC 3.2.1.17 (Muramidase) SB - IM MH - Animals MH - Antigen Presentation/*immunology MH - Antigens, CD/immunology MH - B7-2 Antigen MH - CD40 Antigens/immunology MH - Dendritic Cells/*immunology MH - Female MH - *Lectins, C-Type MH - Lymphocyte Activation/*immunology MH - Lymphocytes/immunology MH - Membrane Glycoproteins/immunology MH - Mice MH - Mice, Inbred C57BL MH - Minor Histocompatibility Antigens MH - Muramidase/immunology MH - Receptors, Cell Surface/immunology MH - Spleen/cytology MH - T-Lymphocytes/*immunology PMC - PMC2195961 EDAT- 2001/09/19 10:00 MHDA- 2001/10/26 10:01 PMCR- 2002/03/17 CRDT- 2001/09/19 10:00 PHST- 2001/09/19 10:00 [pubmed] PHST- 2001/10/26 10:01 [medline] PHST- 2001/09/19 10:00 [entrez] PHST- 2002/03/17 00:00 [pmc-release] AID - 011111 [pii] AID - 10.1084/jem.194.6.769 [doi] PST - ppublish SO - J Exp Med. 2001 Sep 17;194(6):769-79. doi: 10.1084/jem.194.6.769.