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      Dendritic Cells Are Recruited into the Airway Epithelium during the Inflammatory Response to a Broad Spectrum of Stimuli

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          Abstract

          A key rate-limiting step in the adaptive immune response at peripheral challenge sites is the transmission of antigen signals to T cells in regional lymph nodes. Recent evidence suggests that specialized dendritic cells (DC) fulfill this surveillance function in the resting state, but their relatively slow turnover in most peripheral tissues brings into question their effectiveness in signaling the arrival of highly pathogenic sources of antigen which require immediate mobilization of the full range of host defenses for maintenance of homeostasis. However, the present report demonstrates that recruitment of a wave of DC into the respiratory tract mucosa is a universal feature of the acute cellular response to local challenge with bacterial, viral, and soluble protein antigens. Consistent with this finding, we also demonstrate that freshly isolated respiratory mucosal DC respond in vitro to a variety of CC chemokines as well as complementary cleavage products and N-formyl-methionyl-leucine-phenylalanine. This suggests that rapid amplification of specific antigen surveillance at peripheral challenge sites is an integral feature of the innate immune response at mucosal surfaces, and serves as an “early warning system” to alert the adaptive immune system to incoming pathogens.

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          Most cited references 13

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          The immune system evolved to discriminate infectious nonself from noninfectious self.

          Here, Charles Janeway argues that the requirement for two signals to initiate the adaptive immune response may reflect the evolutionary history of host defences. Early phases of host defence involve receptors and ligands that may have controlled immune responses prior to the development of clonally-distributed receptors encoded in rearranging genes. The former receptors persist in contemporary vertebrates both to trigger innate or nonclonal responses and to signal to lymphocytes that a particular antigen is associated with a microorganism.
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            Demonstration and characterization of Ia-positive dendritic cells in the interstitial connective tissues of rat heart and other tissues, but not brain

             D.N. Hart (1981)
            In this study, we have used a mouse monoclonal antibody to rat Ia (RT1- B or class II) antigens to demonstrate, by immunofluorescence on frozen sections, intensely Ia-positive dendritic cells in the interstitial connective tissues of every tissue we have examined (heart, liver, thyroid, pancreas, skin, kidney, ureter, and bladder) with the striking exception of brain. The characteristics of the interstitial dendritic cell found in heart were studied in detail, and this cell was shown to be negative for acid phosphatase, beta-glucuronidase, and ATPase activity, and certainly some and probably all of the cells were negative for nonspecific esterase activity. Experiments with colloidal carbon suggested that the cell was either poorly or not at all phagocytic. The cells were negative for surface immunoglobulin and the W3/13 antigen, but positive for the leukocyte common antigen and the SD (Class I) antigens of the major histocompatibility complex. The cell was shown to be of bone marrow origin, and either the cell itself, or more probably its precursor, was shown to be sensitive to irradiation and to cyclophosphamide. All strains tested--including the nude rat-- had large numbers of interstitial dendritic cells. The widespread distribution, except in brain, of this cell, which resembles in every respect the dendritic cell described by Steinman et al. (4) in the spleen and lymph nodes of the mouse, is of interest, and the implications in this finding are discussed.
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              MHC class II antigen-bearing dendritic cells in pulmonary tissues of the rat. Regulation of antigen presentation activity by endogenous macrophage populations

              Collagenase digestion of tissue slices from perfused, lavaged SPF rat lung released approximately 10(8) viable mononuclear cells per gram tissue, which comprised 35% T lymphocytes and up to 26% macrophages. A subset of these cells that were Ia+, surface Ig-, nonadherent, FcR- and of ultra low density (putative dendritic cells [DC]), presented protein antigen to immune T cells in vitro, and this function was inhibited by the presence of low numbers of endogenous adherent, FcR+ cells (putative macrophages). APCs were also identified in digests from tracheal epithelium, and were shown to bind antigen in immunogenic form as a result of natural (inhalation) exposure in vivo. Immunoperoxidase staining of frozen sections revealed populations of strongly Ia+ cells with prominent DC-like morphology within the alveolar septal walls and the tracheal epithelium; in both areas, they were closely associated with pleiomorphic cells that expressed macrophage surface markers. We accordingly postulate that interactions between Ia+ antigen-presenting DCs and endogenous tissue macrophages play an important role in regulating T cell activity in the respiratory tract.
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                Author and article information

                Journal
                J Exp Med
                The Journal of Experimental Medicine
                The Rockefeller University Press
                0022-1007
                1540-9538
                1 December 1996
                : 184
                : 6
                : 2429-2432
                Affiliations
                From the Division of Cell Biology, TVW Telethon Institute for Child Health Research, West Perth, Western Australia 6872
                Author notes

                Address correspondence to Andrew S. McWilliam or Patrick G. Holt, Division of Cell Biology, TVW Telethon Institute for Child Health Research, PO Box 855, West Perth, Western Australia 6872. T.N.C. Well's present address is Geneva Biomedical Research Institute, Glaxo Wellcome Research & Development, Geneva.

                Article
                2196390
                8976199
                Categories
                Brief Definitive Report
                Brief Definitive Reports

                Medicine

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