| 1. |
- Agace, William, et al.
(author)
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T-lymphocyte-epithelial-cell interactions: integrin alpha(E)(CD103)beta(7), LEEP-CAM and chemokines
- 2000
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In: Current Opinion in Cell Biology. - 0955-0674. ; 12:5, s. 563-568
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Research review (peer-reviewed)abstract
- The epithelia are the avascular layers of cells that cover the environment-exposed surfaces of the body. It appears that T cells localize to selected sites in or adjacent to epithelia via the selective expression of adhesion molecules and chemokine receptors on T cells. These bind to counter-receptors and to chemokines expressed by epithelial cells. Recently, there has been an advance in our understanding of the interaction of the alpha(Ebeta7) integrin with its epithelial cell ligand, E-cadherin. In addition, a new adhesion molecule has been identified on non-intestinal epithelial cells, termed lymphocyte-endothelial-epithelial-cell adhesion molecule (LEEP-CAM). Finally, there have been advances in our understanding of the role of skin- or gut-epithelia-derived chemokines in regulating activated T cell homing to these sites.
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| 2. |
- Ericsson, Anna, et al.
(author)
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CCL25/CCR9 promotes the induction and function of CD103 on intestinal intraepithelial lymphocytes.
- 2004
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In: European Journal of Immunology. - : Wiley. - 1521-4141 .- 0014-2980. ; 34:10, s. 2720-2729
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Journal article (peer-reviewed)abstract
- The integrin CD103 and the chemokine receptor CCR9 are co-expressed on small intestinal CD8+ intraepithelial lymphocytes (IEL), naïve murine CD8+ T cells and by a small population of effector/memory CD8+ T cells, indicating a potential role for CCR9 in regulating CD103 expression and function. Here, we demonstrate that CD103, in contrast to CCR9, is down-regulated on CD8+ T cells following their activation in mesenteric lymph nodes and that effector CD8+ T cells upon initial entry into the small intestinal epithelium are CCR9+CD103-. CD103 was rapidly induced on wild-type CD8+ T cells subsequent to their entry into the small intestinal epithelium, however, CCR9-/- CD8+ T cells exhibited a significant delay in CD103 induction at this site. In addition, the CCR9 ligand, CCL25, that is constitutively expressed in the small intestinal epithelium, induced transient, dose-dependent and pertussis toxin-sensitive CD103-mediated adhesion of CD8+ small intestinal IEL to a murine E-cadherin human Fc (mEFc) fusion protein. Together, these results demonstrate a role for CCR9/CCL25 in promoting the induction and function of CD103 on CD8+ IEL and suggest that this chemokine receptor/chemokine pair may function to regulate lymphocyte-epithelial interactions in the small intestinal mucosa.
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| 3. |
- Ericsson, Anna, et al.
(author)
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CCL25 Enhances CD103-Mediated Lymphocyte Adhesion to E-Cadherin.
- 2004
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In: Annals of the New York Academy of Sciences. - : Wiley. - 0077-8923 .- 1749-6632. ; 1029, s. 334-336
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Journal article (peer-reviewed)abstract
- Our results demonstrate that (1) CD103 is upregulated on CD8(+) T cells subsequent to their entry into the small intestinal epithelium, and (2) that the chemokine CCL25 enhances CD103-mediated adhesion to E-cadherin. These results suggest a novel role for chemokines in modulating interactions between lymphocytes and epithelial cells at mucosal surfaces.
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| 4. |
- Johansson Lindbom, Bengt, et al.
(author)
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Selective Generation of Gut Tropic T Cells in Gut-associated Lymphoid Tissue (GALT): Requirement for GALT Dendritic Cells and Adjuvant.
- 2003
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In: Journal of Experimental Medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 198:6, s. 963-969
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Journal article (peer-reviewed)abstract
- n the current study, we address the underlying mechanism for the selective generation of gut-homing T cells in the gut-associated lymphoid tissues (GALT). We demonstrate that DCs in the GALT are unique in their capacity to establish T cell gut tropism but in vivo only confer this property to T cells in the presence of DC maturational stimuli, including toll-like receptor-dependent and -independent adjuvants. Thus, DCs from mesenteric LNs (MLNs), but not from spleen, supported expression of the chemokine receptor CCR9 and integrin {alpha}4ß7 by activated CD8+ T cells. While DCs were also required for an efficient down-regulation of CD62L, this function was not restricted to MLN DCs. In an adoptive CD8+ T cell transfer model, antigen-specific T cells entering the small intestinal epithelium were homogeneously CCR9+{alpha}4ß7+CD62Llow, and this phenotype was only generated in GALT and in the presence of adjuvant. Consistent with the CCR9+ phenotype of the gut-homing T cells, CCR9 was found to play a critical role in the localization of T cells to the small intestinal epithelium. Together, these results demonstrate that GALT DCs and T cell expression of CCR9 play critical and integrated roles during T cell homing to the gut.
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| 5. |
- Johansson Lindbom, Bengt, et al.
(author)
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Vitamin A helps gut T cells find their way in the dark.
- 2004
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In: Nature Medicine. - : Springer Science and Business Media LLC. - 1546-170X .- 1078-8956. ; 10:12, s. 1300-1301
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Journal article (peer-reviewed)abstract
- Once activated, some T cells home to distinct sites in the body, such as the intestine and inflamed skin. Research in mice shows that dendritic cells in the gut produce a derivative of vitamin A, retinoic acid, that gives T cells directions.
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| 6. |
- Kunkel, E J, et al.
(author)
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Lymphocyte CC chemokine receptor 9 and epithelial thymus-expressed chemokine (TECK) expression distinguish the small intestinal immune compartment: Epithelial expression of tissue-specific chemokines as an organizing principle in regional immunity
- 2000
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In: Journal of Experimental Medicine. - 1540-9538. ; 192:5, s. 761-768
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Journal article (peer-reviewed)abstract
- The immune system has evolved specialized cellular and molecular mechanisms for targeting and regulating immune responses at epithelial surfaces. Here we show that small intestinal intraepithelial lymphocytes and lamina propria lymphocytes migrate to thymus-expressed chemokine (TECK). This attraction is mediated by CC chemokine receptor (CCR)9, a chemoattractant receptor expressed at high levels by essentially all CD4(+) and CD8(+) T lymphocytes in the small intestine. Only a small subset of lymphocytes in the colon are CCR9(+), and lymphocytes from other tissues including tonsils, lung, inflamed liver, normal or inflamed skin, inflamed synovium and synovial fluid, breast milk, and seminal fluid are universally CCR9(-). TECK expression is also restricted to the small intestine: immunohistochemistry reveals that intense anti-TECK reactivity characterizes crypt epithelium in the jejunum and ileum, but not in other epithelia of the digestive tract (including stomach and colon), skin, lung, or salivary gland. These results imply a restricted role for lymphocyte CCR9 and its ligand TECK in the small intestine, and provide the first evidence for distinctive mechanisms of lymphocyte recruitment that may permit functional specialization of immune responses in different segments of the gastrointestinal tract. Selective expression of chemokines by differentiated epithelium may represent an important mechanism for targeting and specialization of immune responses.
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| 7. |
- Marsal, Jan, et al.
(author)
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Involvement of CCL25 (TECK) in the generation of the murine small-intestinal CD8alpha alpha+CD3+ intraepithelial lymphocyte compartment.
- 2002
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In: European Journal of Immunology. - 1521-4141. ; 32:12, s. 3488-3497
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Journal article (peer-reviewed)abstract
- The CC chemokine CCL25 (TECK) is selectively expressed in the thymus and small intestine, indicating a potential role in T lymphocyte development. In the present study we examined the role of CCL25 in the generation of the small-intestinal CD8alpha alpha(+)CD3(+) intraepithelial lymphocyte (IEL) compartment. CCL25 mRNA expression in the murine small intestine increased at three weeks of age and corresponded with the appearance of CD8alpha alpha(+)CD3(+) lymphocytes in the small-intestinal epithelium. Administration of monoclonal neutralizing anti-CCL25 antibody to two-week-old mice led to a approximately 50% reduction in the total number of CD8alpha alpha(+)TCRgamma delta(+) and CD8alpha alpha(+)TCRalpha beta(+) IEL at four weeks of age. Freshly isolated murine CD8alpha alpha(+)CD3(+) IEL migrated in response to CCL25 and expressed the CCL25 receptor, CCR9. Analysis of CCR9 expression on putative IEL precursor populations demonstrated the presence of both CCR9(-) and CCR9(+) cells and indicated that up-regulation of this receptor occurred during IEL precursor differentiation. Finally, data from wild-type and RAG(-/-) mice suggested that the reduction in CD8alpha alpha(+)CD3(+) IEL in anti-CCL25 antibody treated mice resulted primarily from defective maintenance and/or development of IEL precursors rather than a direct effect on mature CD8alpha alpha(+)CD3(+) IEL.
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| 8. |
- Sitnicka Quinn, Ewa, et al.
(author)
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Complementary Signaling through flt3 and Interleukin-7 Receptor {alpha} Is Indispensable for Fetal and Adult B Cell Genesis.
- 2003
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In: Journal of Experimental Medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 198:10, s. 1495-1506
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Journal article (peer-reviewed)abstract
- Extensive studies of mice deficient in one or several cytokine receptors have failed to support an indispensable role of cytokines in development of multiple blood cell lineages. Whereas B1 B cells and Igs are sustained at normal levels throughout life of mice deficient in IL-7, IL-7R{alpha}, common cytokine receptor gamma chain, or flt3 ligand (FL), we report here that adult mice double deficient in IL-7R{alpha} and FL completely lack visible LNs, conventional IgM+ B cells, IgA+ plasma cells, and B1 cells, and consequently produce no Igs. All stages of committed B cell progenitors are undetectable in FL-/- x IL-7R{alpha}-/- BM that also lacks expression of the B cell commitment factor Pax5 and its direct target genes. Furthermore, in contrast to IL-7R{alpha}-/- mice, FL-/- x IL-7R{alpha}-/- mice also lack mature B cells and detectable committed B cell progenitors during fetal development. Thus, signaling through the cytokine tyrosine kinase receptor flt3 and IL-7R{alpha} are indispensable for fetal and adult B cell development.
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| 9. |
- Svensson Frej, Marcus, et al.
(author)
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CCL25 mediates the localization of recently activated CD8alphabeta(+) lymphocytes to the small-intestinal mucosa.
- 2002
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In: Journal of Clinical Investigation. - 0021-9738. ; 110:8, s. 1113-1121
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Journal article (peer-reviewed)abstract
- The recruitment of antigen-specific T lymphocytes to the intestinal mucosa is central to the development of an effective mucosal immune response, yet the mechanism by which this process occurs remains to be fully defined. Here we show that the CC chemokine receptor 9 (CCR9) is selectively and functionally expressed on murine alpha(E)beta(7)(+) naive CD8alphabeta(+) lymphocytes and a subset of recently activated CD69(+) CD8alphabeta(+) lymphocytes. Using a T cell receptor transgenic transfer model, we demonstrate that CCR9 expression is functionally maintained on CD8alphabeta(+) lymphocytes following activation in mesenteric lymph nodes but rapidly downregulated on CD8alphabeta(+) lymphocytes activated in peripheral lymph nodes. These recently activated CCR9(+) CD8alphabeta(+) lymphocytes selectively localized to the small-intestinal mucosa, and in vivo neutralization of the CCR9 ligand, CCL25, reduced the ability of these cells to populate the small-intestinal epithelium. Together these results demonstrate an important role for chemokines in the localization of T lymphocytes to the small-intestinal mucosa and suggest that targeting CCL25 and/or CCR9 may provide a means to selectively modulate small-intestinal immune responses.
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| 10. |
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