Dendritic Cells Induce Peripheral T Cell Unresponsiveness under Steady State Conditions in Vivo

By D. Hawiger, K. Inaba, Yair Dorsett, M. Guo, K. Mahnke, M. Rivera, J. Ravetch, R. Steinman, Michel C. Nussenzweig. Journal of Experimental Medicine, 2001

2,052 citations recorded by the source corpus.

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 γ 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.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/192e6eafca7437732d01b3244a48de88d7acf36c

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Citations in the corpus

The CD8+ Dendritic Cell Subset Selectively Endocytoses Dying Cells in Culture and In Vivo (2002, background): “1300 Uptake of Dying Cells by CD8 DCs In Situ dence for this has recently been obtained in studies of the presentation of an antigenic peptide delivered selectively to DCs in situ via a monoclonal anti–DEC-205 antibody (49).”
Pathophysiology of Cisplatin-Induced Acute Kidney Injury (2014, background): “In clinical practice, various types of cisplatin-induced vascular toxicities can be caused by cisplatin such as thromboticmicroangiopathy andmyocardial infarction.”
In Vivo Instruction of Suppressor Commitment in Naive T Cells (2004, background): “Thus far, it has been demonstrated that Ag presentation by nonactivated DCs can result in recessive tolerance (40, 41), but it is possible that low doses of peptide presented over relatively long time periods (10 d) on nonactivated DCs represents a natural way of inducing active immunosuppression by”
Dendritic-cell-based therapeutic cancer vaccines. (2013, background): “Studies with adoptive T cell transfer showed that effector cells derived from naive CD8 T cells expressed higher CD27 and retained longer telomeres, suggesting that these cells have a greater proliferative potential (Hinrichs et al., 2011; Klebanoff et al., 2012).”
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Homing and cellular traffic in lymph nodes (2003, background): “By contrast, a lymph-borne antibody specific for a cell-surface marker on DCs was shown to accumulate on DCs throughout the T-cell are”
Inducing and expanding regulatory T cell populations by foreign antigen (2005, result): “Although in some studies this mode of peptide delivery resulted in efficient activation and proliferation followed by deletion and/or anergy of residual T cell”
Efficient Targeting of Protein Antigen to the Dendritic Cell Receptor DEC-205 in the Steady State Leads to Antigen Presentation on Major Histocompatibility Complex Class I Products and Peripheral CD8+ T Cell Tolerance (2002, background): “In contrast, DEC-205, an endocytic receptor with 10 membrane-external, contiguous C-type lectin domains (30, 31), mediates the efficient processing and presentation of antigens on MHC class II products in vivo (32).”