Selective Imprinting of Gut-Homing T Cells by Peyer's Patch Dendritic Cells, Nature 424, 88-93

The Center for Blood Research and Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Nature (Impact Factor: 41.46). 08/2003; 424(6944):88-93. DOI: 10.1038/nature01726
Source: PubMed


Whereas naive T cells migrate only to secondary lymphoid organs, activation by antigen confers to T cells the ability to home to non-lymphoid sites. Activated effector/memory T cells migrate preferentially to tissues that are connected to the secondary lymphoid organs where antigen was first encountered. Thus, oral antigens induce effector/memory cells that express essential receptors for intestinal homing, namely the integrin alpha4beta7 and CCR9, the receptor for the gut-associated chemokine TECK/CCL25 (refs 6, 8, 9). Here we show that this imprinting of gut tropism is mediated by dendritic cells from Peyer's patches. Stimulation of CD8-expressing T cells by dendritic cells from Peyer's patches, peripheral lymph nodes and spleen induced equivalent activation markers and effector activity in T cells, but only Peyer's patch dendritic cells induced high levels of alpha4beta7, responsiveness to TECK and the ability to home to the small intestine. These findings establish that Peyer's patch dendritic cells imprint gut-homing specificity on T cells, and thus license effector/memory cells to access anatomical sites most likely to contain their cognate antigen.

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    • "B and T cells primed in mucosal lymphoid tissues express specific adhesion molecules and chemokine receptors that guide them to other mucosal sites after transit through the circulatory system. Thus, exposure to pathogens (or vaccine antigens) at one site can provide protection to mucosal sites systemically (Kunkel and Butcher, 2003; Mora et al., 2003). This phenomenon has important implications for the development of mucosal vaccines since immunization at one site may protect all mucosal and glandular tissues (Mestecky, 1987). "
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    ABSTRACT: Mucosal surfaces are the portals of entry for a wide variety of pathogenic organisms. Vaccines that induce potent antigen-specific mucosal immunity can prevent infections across such surfaces. The success of mucosal vaccines largely depends on the choice of coadministered adjuvant. Cholera toxin and heat labile enterotoxin have been extensively studied for use as mucosal vaccine adjuvants. However, the toxicity associated with these bacterially derived molecules necessitates development of alternative mucosal adjuvants with a good safety profile coupled with potent immunostimulatory activity. Synthetic oligodeoxynucleotides expressing unmethylated CpG motifs represent one such class of emerging mucosal adjuvant and are the focus of this review.
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    • "The chemokine system is an intricate network of related cytokines and their cognate receptors, which together play a key role in the directed migration of leukocytes to their site of action [1] [2]. Expression of both the chemokine receptor CCR9 and the integrin í µí»¼ 4 í µí»½ 7 is required for efficient lymphocyte homing to the intestine; these proteins form the socalled gut-homing phenotype of intestinal lymphocytes [3] [4]. CCR9 is expressed on the majority of CD4 + (67%) and CD8 + (54%) T cells [5] as well as B cells [4] and plasmacytoid dendritic cells [6] [7] isolated from the small intestine. "
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    ABSTRACT: While it has long been established that the chemokine receptor CCR9 and its ligand CCL25 are essential for the movement of leukocytes into the small intestine and the development of small-intestinal inflammation, the role of this chemokine-receptor pair in colonic inflammation is not clear. Toward this end, we compared colonic CCL25 protein levels in healthy individuals to those in patients with ulcerative colitis. In addition, we determined the effect of CCR9 pharmacological inhibition in the mdr1a −/− mouse model of ulcerative colitis. Colon samples from patients with ulcerative colitis had significantly higher levels of CCL25 protein compared to healthy controls, a finding mirrored in the mdr1a −/− mice. In the mdr1a −/− mice, CCR9 antagonists significantly decreased the extent of wasting and colonic remodeling and reduced the levels of inflammatory cytokines in the colon. These findings indicate that the CCR9:CCL25 pair plays a causative role in ulcerative colitis and suggest that CCR9 antagonists will provide a therapeutic benefit in patients with colonic inflammation.
    Full-text · Article · Oct 2015 · Mediators of Inflammation
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    • "It is important to note that we acquired capacitance data from a colony of cells rather than from an individual cell. A single cell can be cultured with a smaller gap design and cell manipulation between electrodes using optical cell trapping [37] [38], or cell imprinting technique [39]. However, the average of data from a Fig. 3. Normalized capacitance difference of L-929 cells treated with different concentration (0; orange, 0.17 ␮M; red, 0.83 ␮M; navy, 3.33 ␮M; dark yellow) of EGF over time. "
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    ABSTRACT: We developed a capacitance sensor with parallel plate geometry to measure epithermal growth factor receptor (EGFR) expression levels on cell membrane in real-time. We first proved correlations between capacitance changes and cell numbers settled down between electrodes, and then observed capacitance changes elicited by interactions between EGFR on membrane and EGF proteins in real time. Consequently, we confirmed that the EGFR expression levels of varied typed cells were successfully quantified. This approach can effectively distinguish differences of EGFR levels of cancer cells and normal cells in real-time. Also, up to 600% sensitivity enhancements and around 2.2 h on average sensing time saving were achieved by using the capacitance sensor over a conventional immunoassay technique. Such a capacitance biosensor can be extended to broad fields where the receptor–antibody reactions, the receptor–virus reactions or DNA hybridizations are involved.
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