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      Dendritic cells in the T-cell areas of lymphoid organs

      , ,
      Immunological Reviews
      Wiley

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          Abstract

          Substantial numbers of dendritic cells (DCs) are found in the T-cell areas of peripheral lymphoid organs such as the spleen, lymph node and Peyer's patch. By electron microscopy these DCs (also called interdigitating cells) form a network through which T-cells continually recirculate. The cytological features of DCs in the T-cell areas, as well as a number of markers detected with monoclonal antibodies, are similar to mature DCs that develop from other sites such as skin and bone marrow. Some markers that are expressed in abundance are: MHC II and the associated invariant chain, accessory molecules such as CD40 and CD86, a multilectin receptor for antigen presentation called DEC-205, the integrin CD11c, several antigens within the endocytic system that are detected by monoclonal antibodies but are as yet uncharacterized at the molecular level, and, in the human system, molecules termed S100b, CD83 and p55. DCs in the periphery can pick up antigens and migrate to the T-cell areas to initiate immunity. However, there are new observations that DCs within the T-cell areas also express high levels of self-antigens and functional fas-ligand capable of inducing CD4+ T-cell death. We speculate that there are at least 2 sets of DCs in the T-cell areas, a migratory myeloid pathway that brings in antigens from the periphery and induces immunity, and a more resident lymphoid pathway that presents self-antigens and maintains tolerance.

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          Most cited references112

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          Ligation of CD40 on dendritic cells triggers production of high levels of interleukin-12 and enhances T cell stimulatory capacity: T-T help via APC activation

          We investigated the possibility that T helper cells might enhance the stimulatory function of dendritic cells (DCs). We found that ligation of CD40 by CD40L triggers the production of extremely high levels of bioactive IL-12. Other stimuli such as microbial agents, TNF-alpha or LPS are much less effective or not at all. In addition, CD40L is the most potent stimulus in upregulating the expression of ICAM-1, CD80, and CD86 molecules on DCs. These effects of CD40 ligation result in an increased capacity of DCs to trigger proliferative responses and IFN- gamma production by T cells. These findings reveal a new role for CD40- CD40L interaction in regulating DC function and are relevant to design therapeutic strategies using cultured DCs.
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            The receptor DEC-205 expressed by dendritic cells and thymic epithelial cells is involved in antigen processing.

            Dendritic cells and thymic epithelial cells perform important immunoregulatory functions by presenting antigens in the form of peptides bound to cell-surface major histocompatibility complex (MHC) molecules to T cells. Whereas B cells are known to present specific antigens efficiently through their surface immunoglobins, a comparable mechanism for the capture and efficient presentation of diverse antigens by dendritic cells and thymic epithelial cells has not previously been described. We show here that their antigen-presentation function is associated with the high-level expression of DEC-205, an integral membrane protein homologous to the macrophage mannose receptor and related receptors which are able to bind carbohydrates and mediate endocytosis. DEC-205 is rapidly taken up by means of coated pits and vesicles, and is delivered to a multivesicular endosomal compartment that resembles the MHC class II-containing vesicles implicated in antigen presentation. Rabbit antibodies that bind DEC-205 are presented to reactive T-cell hybridomas 100-fold more efficiently than rabbit antibodies that do not bind DEC-205. Thus DEC-205 is a novel endocytic receptor that can be used by dendritic cells and thymic epithelial cells to direct captured antigens from the extracellular space to a specialized antigen-processing compartment.
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              Expression of relB is required for the development of thymic medulla and dendritic cells.

              Dendritic cells (DC) derived from bone marrow are critical in the function of the immune system, for they are the primary antigen-presenting cells in the activation of T-lymphocyte response. Their differentiation from precursor cells has not been defined at a molecular level, but recent studies have shown an association between expression of the relB subunit of the NF-kappa B complex and the presence of DC in specific regions of normal unstimulated lymphoid tissues. Here we show that relB expression also correlates with differentiation of DC in autoimmune infiltrates in situ, and that a mutation disrupting the relB gene results in mice with impaired antigen-presenting cell function, and a syndrome of excess production of granulocytes and macrophages. Thymic UEA-1+ medullary epithelial cells from normal mice show striking similarities to DC and, interestingly, these cells are also absent in relB mutant mice. Taken together, these results suggest that relB is critical in the coordinated activation of genes necessary for the differentiation of two unrelated but phenotypically similar cells (DC and thymic UEA-1+ medullary epithelial cells) and is therefore a candidate for a gene determining lineage commitment in the immune system.
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                Author and article information

                Journal
                Immunological Reviews
                Immunol Rev
                Wiley
                0105-2896
                1600-065X
                April 1997
                April 1997
                : 156
                : 1
                : 25-37
                Article
                10.1111/j.1600-065X.1997.tb00956.x
                9176697
                9588bbf1-9b92-4205-b798-83092bcd04a7
                © 1997

                http://doi.wiley.com/10.1002/tdm_license_1.1

                History

                Molecular medicine,Neurosciences
                Molecular medicine, Neurosciences

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