scholarly journals Recirculation and homing of lymphocyte subsets: dual homing specificity of beta 7-integrin(high)-lymphocytes in nonobese diabetic mice

Blood ◽  
1996 ◽  
Vol 88 (3) ◽  
pp. 934-944 ◽  
Author(s):  
A Hanninen ◽  
M Salmi ◽  
O Simell ◽  
D Andrew ◽  
S Jalkanen
Keyword(s):  
Immune System ◽  
Nod Mice ◽  
Intraepithelial Lymphocytes ◽  
Mucosal Immune System ◽  
Lymphoid Tissues ◽  
Integrin Subunit ◽  
Homing Receptor ◽  
Functional Studies ◽  
Peripheral Lymph ◽  
Nonobese Diabetic Mice

Abstract The beta 7-integrin subunit can pair with two alpha-chains, alpha 4 and alpha E, and is expressed mainly on lymphocytes. As an alpha 4- heterodimer it binds to the mucosal addressin MAdCAM-1, thus acting as a mucosal homing receptor. As an alpha E-heterodimer it binds to E- cadherin and is mainly found on intestinal intraepithelial lymphocytes. Consequently, beta 7 is mostly expressed on lymphocytes of the mucosal immune system. To study the compartmentalization of these cells further we compared the distribution of such lymphocytes in two strains of mice (BALB/c and NOD) and found that the distribution of beta 7-positive lymphocytes among various lymphoid tissues in these strains was very different. In NOD mice a conspicuous population of beta 7- integrin(high) lymphocytes expressing either alpha 4, alpha E, or both, was found in nonmucosal lymphoid tissues such as peripheral lymph nodes (PLNs). They mostly expressed the PLN homing receptor L-selectin, and included both naive and memory cells on the basis of their expression of CD44/pgp-1 and CD45RB, as did the few beta 7(high) lymphocytes in BALB/c PLNs. Their homing to Peyer's patches (PPs) and PLNs was equally effective and the cells homing to PPs and PLNs were equal in their level of L-selectin and alpha 4/beta 7 expression. However, functional studies indicated that their homing to PPs mostly depended on alpha 4/beta 7-integrin, whereas they mainly used L-selectin to home to PLNs. beta 7(high) lymphocytes were found also in circulating blood of unmanipulated NOD mice, and their L-selectin expression was higher than in BALB/c mice. These results show that lymphocytes of the mucosal immune system may also express the peripheral node homing receptor L- selectin during their recirculation and that in NOD mice they frequently retain a dual homing specificity, which leads to their accumulation in nonmucosal tissues.

scholarly journals Recirculation and homing of lymphocyte subsets: dual homing specificity of beta 7-integrin(high)-lymphocytes in nonobese diabetic mice

Blood ◽  
1996 ◽  
Vol 88 (3) ◽  
pp. 934-944
Author(s):  
A Hanninen ◽  
M Salmi ◽  
O Simell ◽  
D Andrew ◽  
S Jalkanen
Keyword(s):  
Immune System ◽  
Nod Mice ◽  
Intraepithelial Lymphocytes ◽  
Mucosal Immune System ◽  
Lymphoid Tissues ◽  
Integrin Subunit ◽  
Homing Receptor ◽  
Functional Studies ◽  
Peripheral Lymph ◽  
Nonobese Diabetic Mice

The beta 7-integrin subunit can pair with two alpha-chains, alpha 4 and alpha E, and is expressed mainly on lymphocytes. As an alpha 4- heterodimer it binds to the mucosal addressin MAdCAM-1, thus acting as a mucosal homing receptor. As an alpha E-heterodimer it binds to E- cadherin and is mainly found on intestinal intraepithelial lymphocytes. Consequently, beta 7 is mostly expressed on lymphocytes of the mucosal immune system. To study the compartmentalization of these cells further we compared the distribution of such lymphocytes in two strains of mice (BALB/c and NOD) and found that the distribution of beta 7-positive lymphocytes among various lymphoid tissues in these strains was very different. In NOD mice a conspicuous population of beta 7- integrin(high) lymphocytes expressing either alpha 4, alpha E, or both, was found in nonmucosal lymphoid tissues such as peripheral lymph nodes (PLNs). They mostly expressed the PLN homing receptor L-selectin, and included both naive and memory cells on the basis of their expression of CD44/pgp-1 and CD45RB, as did the few beta 7(high) lymphocytes in BALB/c PLNs. Their homing to Peyer's patches (PPs) and PLNs was equally effective and the cells homing to PPs and PLNs were equal in their level of L-selectin and alpha 4/beta 7 expression. However, functional studies indicated that their homing to PPs mostly depended on alpha 4/beta 7-integrin, whereas they mainly used L-selectin to home to PLNs. beta 7(high) lymphocytes were found also in circulating blood of unmanipulated NOD mice, and their L-selectin expression was higher than in BALB/c mice. These results show that lymphocytes of the mucosal immune system may also express the peripheral node homing receptor L- selectin during their recirculation and that in NOD mice they frequently retain a dual homing specificity, which leads to their accumulation in nonmucosal tissues.

scholarly journals The role of gut-associated lymphoid tissues and mucosal defence

2005 ◽  
Vol 93 (S1) ◽  
pp. S41-S48 ◽  
Author(s):  
Maria Luisa Forchielli ◽  
W. Allan Walker
Keyword(s):  
Immune System ◽  
Breast Milk ◽  
Gastrointestinal Disease ◽  
Bacterial Colonization ◽  
Adaptive Immune Response ◽  
Atopic Disease ◽  
Mucosal Immune System ◽  
Bacterial Invasion ◽  
Lymphoid Tissues ◽  
Protective Function

The newborn infant leaves a germ-free intrauterine environment to enter a contaminated extrauterine world and must have adequate intestinal defences to prevent the expression of clinical gastrointestinal disease states. Although the intestinal mucosal immune system is fully developed after a full-term birth, the actual protective function of the gut requires the microbial stimulation of initial bacterial colonization. Breast milk contains prebiotic oligosaccharides, like inulin-type fructans, which are not digested in the small intestine but enter the colon as intact large carbohydrates that are then fermented by the resident bacteria to produce SCFA. The nature of this fermentation and the consequent pH of the intestinal contents dictate proliferation of specific resident bacteria. For example, breast milk-fed infants with prebiotics present in breast milk produce an increased proliferation of bifidobacteria and lactobacilli (probiotics), whereas formula-fed infants produce more enterococci and enterobacteria. Probiotics, stimulated by prebiotic fermentation, are important to the development and sustainment of intestinal defences. For example, probiotics can stimulate the synthesis and secretion of polymeric IgA, the antibody that coats and protects mucosal surfaces against harmful bacterial invasion. In addition, appropriate colonization with probiotics helps to produce a balanced T helper cell response (Th1 = Th2 = Th3/Tr1) and prevent an imbalance (Th1 > Th2 or Th2 > Th1) contributing in part to clinical disease (Th2 imbalance contributes to atopic disease and Th1 imbalance contributes to Crohn's disease andHelicobacter pylori-induced gastritis). Furthermore, a series of pattern recognition receptors, toll-like receptors on gut lymphoid and epithelial cells that interact with bacterial molecular patterns (e.g. endotoxin (lipopolysaccharide), flagellin, etc.), help modulate intestinal innate immunity and an appropriate adaptive immune response. Animal and clinical studies have shown that inulin-type fructans will stimulate an increase in probiotics (commensal bacteria) and these bacteria have been shown to modulate the development and persistence of appropriate mucosal immune responses. However, additional studies are needed to show that prebiotics can directly or indirectly stimulate intestinal host defences. If this can be demonstrated, then prebiotics can be used as a dietary supplement to stimulate a balanced and an appropriately effective mucosal immune system in newborns and infants.

scholarly journals Targeting the Gut Mucosal Immune System Using Nanomaterials

Pharmaceutics ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1755
Author(s):  
Jacob McCright ◽  
Ann Ramirez ◽  
Mayowa Amosu ◽  
Arnav Sinha ◽  
Amanda Bogseth ◽  
...  
Keyword(s):  
Immune System ◽  
The Body ◽  
Mucosal Immune System ◽  
Lymphoid Tissues ◽  
Gi Tract ◽  
Public Health Burden ◽  
Intestinal Infections ◽  
Significant Public Health ◽  
Inflammatory Processes ◽  
Gi Inflammation

The gastrointestinal (GI) tract is one the biggest mucosal surface in the body and one of the primary targets for the delivery of therapeutics, including immunotherapies. GI diseases, including, e.g., inflammatory bowel disease and intestinal infections such as cholera, pose a significant public health burden and are on the rise. Many of these diseases involve inflammatory processes that can be targeted by immune modulatory therapeutics. However, nonspecific targeting of inflammation systemically can lead to significant side effects. This can be avoided by locally targeting therapeutics to the GI tract and its mucosal immune system. In this review, we discuss nanomaterial-based strategies targeting the GI mucosal immune system, including gut-associated lymphoid tissues, tissue resident immune cells, as well as GI lymph nodes, to modulate GI inflammation and disease outcomes, as well as take advantage of some of the primary mechanisms of GI immunity such as oral tolerance.

Sa.83. Impairment of Gut Mucosa and Gut Mucosal Immune System in NOD Mice: Gut Mucosa as a Gateway for Autoimmunity in Type 1 Diabetes

2008 ◽  
Vol 127 ◽  
pp. S107-S108
Author(s):  
David Funda ◽  
Hana Kozakova ◽  
Milan Jirsa ◽  
Anne Kaas ◽  
Petra Fundova ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Immune System ◽  
Nod Mice ◽  
Mucosal Immune System ◽  
Gut Mucosa

scholarly journals The human peripheral lymph node vascular addressin is a ligand for LECAM-1, the peripheral lymph node homing receptor.

1991 ◽  
Vol 114 (2) ◽  
pp. 343-349 ◽  
Author(s):  
E L Berg ◽  
M K Robinson ◽  
R A Warnock ◽  
E C Butcher
Keyword(s):  
Lymph Node ◽  
Lymphoid Tissues ◽  
Dependent Manner ◽  
Peripheral Lymph Node ◽  
Lymphocyte Homing ◽  
High Endothelial Venules ◽  
Homing Receptor ◽  
Calcium Dependent ◽  
Lymph Node Homing ◽  
Peripheral Lymph

The trafficking of lymphocytes from the blood and into lymphoid organs is controlled by tissue-selective lymphocyte interactions with specialized endothelial cells lining post capillary venules, in particular the high endothelial venules (HEV) found in lymphoid tissues and sites of chronic inflammation. Lymphocyte interactions with HEV are mediated in part by lymphocyte homing receptors and tissue-specific HEV determinants, the vascular addressins. A peripheral lymph node addressin (PNAd) has been detected immunohistologically in mouse and man by monoclonal antibody MECA-79, which inhibits lymphocyte homing to lymph nodes and lymphocyte binding to lymph node and tonsillar HEV. The human MECA-79 antigen, PNAd, is molecularly distinct from the 65-kD mucosal vascular addressin. The most abundant iodinated species by SDS-PAGE is 105 kD. When affinity isolated and immobilized on glass slides, MECA-79 immunoisolated material binds human and mouse lymphocytes avidly in a calcium dependent manner. Binding is blocked by mAb MECA-79, by antibodies against mouse or human LECAM-1 (the peripheral lymph node homing receptor, the MEL-14 antigen, LAM-1), and by treatment of PNAd with neuraminidase. Expression of LECAM-1 cDNA confers PNAd binding ability on a transfected B cell line. We conclude that LECAM-1 mediates lymphocyte binding to PNAd, an interaction that involves the lectin activity of LECAM-1 and carbohydrate determinants on the addressin.

Effective Mucosal Immunity: Current Concepts for Vaccine Delivery and Immune Response Analysis

1994 ◽  
Vol 10 (1) ◽  
pp. 93-106 ◽  
Author(s):  
Jerry R. McGhee ◽  
Hiroshi Kiyono
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Mucosal Immunity ◽  
Vaccine Delivery ◽  
Mucosal Immune System ◽  
Response Analysis ◽  
Lymphoid Tissues ◽  
Separate Entity

AbstractIt is now established that the mucosal immune system is a separate entity and is regulated in a different fashion than that in peripheral lymphoid tissues (the systemic immune system). In this brief review, five selected areas within the field of mucosal immunity are discussed in the context of the goals for vaccines for the Children's Vaccine Initiative.

scholarly journals Characterization of a human homologue of the murine peripheral lymph node homing receptor.

1989 ◽  
Vol 109 (1) ◽  
pp. 421-427 ◽  
Author(s):  
B R Bowen ◽  
T Nguyen ◽  
L A Lasky
Keyword(s):  
Cell Adhesion ◽  
Lymph Node ◽  
Adhesion Molecule ◽  
Carbohydrate Binding ◽  
Human Homologue ◽  
Peripheral Lymph Node ◽  
Homing Receptor ◽  
Lymph Node Homing ◽  
Peripheral Lymph ◽  
Human Receptor

Lymphocyte trafficking is a fundamental aspect of the immune system that allows B and T lymphocytes with diverse antigen recognition specificities to be exposed to various antigenic stimuli in spatially distinct regions of an organism. A lymphocyte adhesion molecule that is involved with this trafficking phenomenon has been termed the homing receptor. Previous work (Lasky, L., T. Yednock, M. Singer, D. Dowbenko, C. Fennie, H. Rodriguez, T. Nguyen, S. Stachel, and S. Rosen. 1989. Cell. 56:1045-1055) has characterized a cDNA clone encoding a murine homing receptor that is involved in trafficking of lymphocytes to peripheral lymph nodes. This molecule was found to contain a number of protein motifs, the most intriguing of which was a carbohydrate binding domain, or lectin, that is apparently involved in the adhesive interaction between murine lymphocytes and peripheral lymph node endothelium. In this study, we have used the murine cDNA clone to isolate a human homologue of this peripheral lymph node-specific adhesion molecule. The human receptor was found to be highly homologous to the murine receptor in overall sequence, but showed no sequence similarity to another surface protein that may be involved with human lymphocyte homing, the Hermes glycoprotein. The extracellular region of the human receptor contained an NH2 terminally located carbohydrate binding domain followed by an EGF-like domain and a domain containing two repeats of a complement binding motif. Transient cell transfection assays using the human receptor cDNA showed that it encoded a surface glycoprotein that cross reacted with a polyclonal antibody directed against the murine peripheral lymph node homing receptor. Interestingly, the human receptor showed a high degree of sequence homology to another human cell adhesion glycoprotein, the endothelial cell adhesion molecule ELAM.

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