A5054888474- Cell Adhesion Molecules Research
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Monoclonal and Polyclonal Antibodies Research
- Chemokine receptors and signaling
- Immunodeficiency and Autoimmune Disorders
- Immune Response and Inflammation
- Mast cells and histamine
- Platelet Disorders and Treatments
- Ear Surgery and Otitis Media
- Glycosylation and Glycoproteins Research
- Fish Ecology and Management Studies
- Diabetes and associated disorders
- Galectins and Cancer Biology
- CAR-T cell therapy research
- Signaling Pathways in Disease
- Psoriasis: Treatment and Pathogenesis
- Coastal wetland ecosystem dynamics
- Ear and Head Tumors
- Clinical practice guidelines implementation
- Wnt/β-catenin signaling in development and cancer
- Cytokine Signaling Pathways and Interactions
- Tuberculosis Research and Epidemiology
- Electronic Health Records Systems
California Department of Fish and Wildlife
2024
University of California, Davis
2022
Harvard University
1996-2012
University of Nebraska Medical Center
2007
Stanford University
1998-2007
Mayo Clinic in Arizona
2007
Brigham and Women's Hospital
1993-2006
ENT and Allergy
1999-2001
UConn Health
1999
University of Cologne
1999
The immune system has evolved specialized cellular and molecular mechanisms for targeting regulating responses at epithelial surfaces. Here we show that small intestinal intraepithelial lymphocytes lamina propria migrate to thymus-expressed chemokine (TECK). This attraction is mediated by CC receptor (CCR)9, a chemoattractant expressed high levels essentially all CD4+ CD8+ T in the intestine. Only subset of colon are CCR9+, from other tissues including tonsils, lung, inflamed liver, normal...
The germline repertoire of variable genes for the TCR-gamma/delta is limited. This, together with availability several V delta-specific and a C mAbs, has made it possible to assess differences in man. cells expressing particular gene segments have been previously shown be localized different anatomical sites. In this study, analysis segment usage performed on subjects from time birth through adulthood revealed striking age-related changes peripheral blood. delta 1+ gamma/delta T predominated...
TECK (thymus-expressed chemokine), a recently described CC chemokine expressed in thymus and small intestine, was found to mediate chemotaxis of human G protein-coupled receptor GPR-9-6/L1.2 transfectants. This activity blocked by anti-GPR-9-6 monoclonal antibody (mAb) 3C3. GPR-9-6 is on subset memory alpha4beta7(high) intestinal trafficking CD4 CD8 lymphocytes. In addition, all lamina propria intraepithelial lymphocytes express GPR-9-6. contrast, not displayed cutaneous lymphocyte...
The integrin CD103 is highly expressed at mucosal sites, but its role in immune regulation remains poorly understood. We have analyzed the functional of intestinal using T cell transfer model colitis. Our results show no mandatory for expression on cells either development or CD4+CD25+ regulatory (T reg) cell–mediated control However, wild-type were unable to prevent colitis immune-deficient recipients lacking CD103, demonstrating a nonredundant host reg regulation. Non–T restricted...
Abstract The mucosal lymphocyte integrin αE(CD103)β7 is thought to be important for intraepithelial (IEL) localization or function. We cloned the murine gene encoding αE, localized it chromosome 11, and generated αE-deficient mice. In αE−/− mice, intestinal vaginal IEL numbers were reduced, consistent with known binding of αEβ7 E-cadherin expressed on epithelial cells. However, was surprising that lamina propria T diminished, as not in propria. contrast, peribronchial, intrapulmonary,...
Abstract Intestinal intraepithelial lymphocytes (iIEL) are a distinct subpopulation of T diffusely distributed in the epithelium. Because > 95% these iIEL express integrin alpha E beta 7, we reasoned that this might mediate localization to We report cultured bound mucosal epithelial cells derived from either breast or intestine. This binding was dependent on presence divalent cations, and blocked by mAb specific for two integrins, 7 L 2. After TGF-beta 1 treatment, cell lines...
Mast cells (MCs) are centrally important in allergic inflammation of the airways, as well intestinal immune response to helminth infection. A single lineage bone marrow (BM)-derived progenitors emigrates from circulation and matures into phenotypically distinct MCs different tissues. Because mechanisms MC progenitor (MCp) homing peripheral tissues have not been evaluated, we used limiting dilution analysis measure concentration MCp various mice deficient for candidate molecules. were almost...
The heterodimeric protein complex recognized by the human mucosal lymphocyte 1 (HML-1) monoclonal antibody is expressed on 95% of intraepithelial lymphocytes but only 1-2% peripheral blood [Cerf-Bensusson, N., Jarry, A., Brousse, Lisowska-Grospierre, B., Guy-Grand, D. & Griscelli, C. (1987) Eur. J. Immunol. 17, 1279-1285]. We purified smaller HML-1 subunit (105 kDa under nonreducing conditions) from hairy-cell leukemia cells and determined N-terminal amino acid sequence this chain. 17...
The cadherins are a family of homophilic adhesion molecules that play vital role in the formation cellular junctions and tissue morphogenesis. Members integrin also involved cell to adhesion, but bind heterophilically immunoglobulin superfamily such as intracellular molecule (ICAM)–1, vascular (VCAM)–1, or mucosal addressin (MadCAM)–1. Recently, an interaction between epithelial (E-) cadherin lymphocyte integrin, αEβ7, has been proposed. Here, we demonstrate human E-cadherin–Fc fusion...
The requirement of β7 integrins for lymphocyte migration was examined during an ongoing immune response in vivo. Transgenic mice (OT-I) expressing ovalbumin-specific major histocompatibility complex class I–restricted T cell receptor antigen were rendered deficient expression all or only the αEβ7 integrin. To quantitate relative use vivo, equal numbers OT-I and OT-I-β7−/− OT-I-αE−/− lymph node (LN) cells adoptively transferred to normal mice. Although LN migrated mesenteric peripheral as...
The SAGE (Standards-Based Active Guideline Environment) project was formed to create a methodology and infrastructure required demonstrate integration of decision-support technology for guideline-based care in commercial clinical information systems. This paper describes the development innovative features Model reports our experience encoding four guidelines. Innovations include methods integrating decision support with workflow employment enterprise order sets. Using SAGE, clinician...
To determine which chemokine receptors might be involved in T lymphocyte localization to the intestinal mucosa, we examined receptor expression on human lamina propria lymphocytes (LPL), intraepithelial (IEL) and CD45RO+β7hi gut homing peripheral blood (PBL). Virtually all LPL IEL expressed CXCR3 CCR5, that have been associated with Th1(Tc1) / Th0 lymphocytes, while CCR3 CCR4, Th2 (Tc2) CCR7, CXCR1 CXCR2 were not expressed. CCR5 functional, as migrated their respective ligands I-TAC RANTES....
Abstract Little is known about the gamma delta T cells in human neonatal umbilical cord blood. To compare blood and adult cells, we studied V gene segment usage these populations by flow cytometry, derived cell clones to determine their functional capabilities. Unlike that predominantly express 2V 2 TCRs, expressed diverse segments paired a variety of combinations rarely observed adults. from similarly array TCRs. These blood-derived had weak cytolytic activity when assayed for K562 tumor...
The mechanisms by which CD8 effector populations interact with epithelial layers is a poorly defined aspect of adaptive immunity. Recognition that effectors have the capacity to express CD103, an integrin directed cell-specific ligand E-cadherin, potentially provides insight into such interactions. To assess role CD103 in promoting CD8-mediated destruction layers, we herein examined mice targeted disruption reject pancreatic islet allografts. Wild-type hosts uniformly rejected allografts,...
The human mucosal lymphocyte-1 (HML-1) antigen is expressed on a subclass of T-lymphocytes known as intra-epithelial lymphocytes which are located between epithelial cells. HML-1 complex to mediate adhesion cell monolayers in vitro. We and others have shown that the an integrin composed beta 7 subunit association with novel alpha subunit, E. Here we report cloning E cDNA its primary amino acid sequence. contained inserted or I domain was more homologous other containing integrins than...
The cell surface heterodimer VLA-4 (alpha 4 beta 1), a member of the integrin family adhesion receptors, is involved in both cell-extracellular matrix and cell-cell adhesion. Unlike any other alpha subunit, intact (150 kDa) subunit can sometimes be cleaved into two noncovalently associated fragments (80 70 kDa). Using biosynthetic mixing experiments, we found that human cleavage regulated, compartmentalized event, occurring soon after maturation 1-associated subunit. Cleavage 4, which...
A subpopulation of the CD3+ peripheral T lymphocytes express TCR-gamma/delta complex. Three distinct TCR-gamma forms that differ in size and ability to form a disulfide bridge with TCR-delta subunit have been described. In this study we analyze structural difference between non-disulfide-linked 55-kD 40-kD chains. The contains smaller polypeptide backbone carries less carbohydrate compared form. cDNA clone corresponding lacks one copy second exon constant region is present other subunit....