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      Tolerogenic dendritic cells.

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          Abstract

          Dendritic cells (DCs) have several functions in innate and adaptive immunity. In addition, there is increasing evidence that DCs in situ induce antigen-specific unresponsiveness or tolerance in central lymphoid organs and in the periphery. In the thymus DCs generate tolerance by deleting self-reactive T cells. In peripheral lymphoid organs DCs also induce tolerance to antigens captured by receptors that mediate efficient uptake of proteins and dying cells. Uptake by these receptors leads to the constitutive presentation of antigens on major histocompatibility complex (MHC) class I and II products. In the steady state the targeting of DC antigen capture receptors with low doses of antigens leads to deletion of the corresponding T cells and unresponsiveness to antigenic rechallenge with strong adjuvants. In contrast, if a stimulus for DC maturation is coadministered with the antigen, the mice develop immunity, including interferon-gamma-secreting effector T cells and memory T cells. There is also new evidence that DCs can contribute to the expansion and differentiation of T cells that regulate or suppress other immune T cells. One possibility is that distinct developmental stages and subsets of DCs and T cells can account for the different pathways to peripheral tolerance, such as deletion or suppression. We suggest that several clinical situations, including autoimmunity and certain infectious diseases, can be influenced by the antigen-specific tolerogenic role of DCs.

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          Author and article information

          Journal
          Annu Rev Immunol
          Annual review of immunology
          Annual Reviews
          0732-0582
          0732-0582
          2003
          : 21
          Affiliations
          [1 ] Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, New York 10021-6399, USA. steinma@mail.rockefeller.edu
          Article
          120601.141040
          10.1146/annurev.immunol.21.120601.141040
          12615891
          910de50a-f4a2-4c5c-ae26-8dbd1065961f
          History

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