scholarly journals Lymphocyte Homing to Bronchus-associated Lymphoid Tissue (BALT) Is Mediated by L-selectin/PNAd, α4β1 Integrin/VCAM-1, and LFA-1 Adhesion Pathways

2003 ◽  
Vol 197 (10) ◽  
pp. 1255-1267 ◽  
Author(s):  
Baohui Xu ◽  
Norbert Wagner ◽  
Linh Nguyen Pham ◽  
Vincent Magno ◽  
Zhongyan Shan ◽  
...  
Keyword(s):  
Immune Responses ◽  
Lymphoid Tissue ◽  
Lymphoid Tissues ◽  
Lymphocyte Migration ◽  
High Endothelial Venules ◽  
Level Of Involvement ◽  
Selectin Ligand ◽  
High Level ◽  
Migration Pathways ◽  
B And T Lymphocytes

Bronchus-associated lymphoid tissue (BALT) participates in airway immune responses. However, little is known about the lymphocyte–endothelial adhesion cascades that recruit lymphocytes from blood into BALT. We show that high endothelial venules (HEVs) in BALT express substantial levels of VCAM-1, in marked contrast to HEVs in other secondary lymphoid tissues. BALT HEVs also express the L-selectin ligand PNAd. Anti–L-selectin, anti-PNAd, and anti–LFA-1 mAbs almost completely block the homing of B and T lymphocytes into BALT, whereas anti–α4 integrin and anti–VCAM-1 mAbs inhibit homing by nearly 40%. α4β7 integrin and MAdCAM-1 are not involved. Importantly, we found that mAbs against α4 integrin and VCAM-1 significantly block the migration of total T cells (80% memory phenotype) but not naive T and B cells to BALT. These results suggest that an adhesion cascade, which includes L-selectin/PNAd, α4β1 integrin/VCAM-1, and LFA-1, targets specific lymphocyte subsets to BALT. This high level of involvement of α4β1 integrin/VCAM-1 is unique among secondary lymphoid tissues, and may help unify lymphocyte migration pathways and immune responses in BALT and other bronchopulmonary tissues.

scholarly journals Id2-, RORγt-, and LTβR-independent initiation of lymphoid organogenesis in ocular immunity

2009 ◽  
Vol 206 (11) ◽  
pp. 2351-2364 ◽  
Author(s):  
Takahiro Nagatake ◽  
Satoshi Fukuyama ◽  
Dong-Young Kim ◽  
Kaoru Goda ◽  
Osamu Igarashi ◽  
...  
Keyword(s):  
Immune Responses ◽  
Lymphoid Tissue ◽  
Orphan Receptor ◽  
Lymphoid Tissues ◽  
Lacrimal Sac ◽  
Antigen Uptake ◽  
Germ Free ◽  
Inhibitor Of Dna Binding ◽  
Lymphoid Organogenesis ◽  
Ocular Immunity

The eye is protected by the ocular immunosurveillance system. We show that tear duct–associated lymphoid tissue (TALT) is located in the mouse lacrimal sac and shares immunological characteristics with mucosa-associated lymphoid tissues (MALTs), including the presence of M cells and immunocompetent cells for antigen uptake and subsequent generation of mucosal immune responses against ocularly encountered antigens and bacteria such as Pseudomonas aeruginosa. Initiation of TALT genesis began postnatally; it occurred even in germ-free conditions and was independent of signaling through organogenesis regulators, including inhibitor of DNA binding/differentiation 2, retinoic acid–related orphan receptor γt, lymphotoxin (LT) α1β2–LTβR, and lymphoid chemokines (CCL19, CCL21, and CXCL13). Thus, TALT shares immunological features with MALT but has a distinct tissue genesis mechanism and plays a key role in ocular immunity.

scholarly journals Essential role of peripheral node addressin in lymphocyte homing to nasal-associated lymphoid tissues and allergic immune responses

2011 ◽  
Vol 208 (5) ◽  
pp. 1015-1025 ◽  
Author(s):  
Yukari Ohmichi ◽  
Jotaro Hirakawa ◽  
Yasuyuki Imai ◽  
Minoru Fukuda ◽  
Hiroto Kawashima
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Specific Ige ◽  
Treg Cells ◽  
Lymphoid Tissues ◽  
Lymphocyte Homing ◽  
Double Knockout ◽  
High Endothelial Venules ◽  
Peripheral Node

Nasal-associated lymphoid tissue (NALT) is a mucosal immune tissue that provides immune responses against inhaled antigens. Lymphocyte homing to NALT is mediated by specific interactions between lymphocytes and high endothelial venules (HEVs) in NALT. In contrast to HEVs in other mucosal lymphoid tissues, NALT HEVs strongly express peripheral node addressins (PNAds) that bear sulfated glycans recognized by the monoclonal antibody MECA-79. We investigated the role of PNAd in lymphocyte homing to NALT using sulfotransferase N-acetylglucosamine-6-O-sulfotransferase (GlcNAc6ST) 1 and GlcNAc6ST-2 double knockout (DKO) mice. The expression of PNAd in NALT HEVs was eliminated in DKO mice. Short-term homing assays indicated that lymphocyte homing to NALT was diminished by 90% in DKO mice. Production of antigen-specific IgE and the number of sneezes in response to nasally administered ovalbumin were also substantially diminished. Consistently, the NALT of DKO mice showed reduced production of IL-4 and increased production of IL-10 together with an increase in CD4+CD25+ regulatory T cells (Treg cells). Compared with the homing of CD4+CD25− conventional T cells, the homing of CD4+CD25+ Treg cells to NALT was less dependent on the L-selectin–PNAd interaction but was partially dependent on PSGL-1 (P-selectin glycoprotein ligand 1) and CD44. These results demonstrate that PNAd is essential for lymphocyte homing to NALT and nasal allergic responses.

scholarly journals Host Transcriptional Response to Persistent Infection with a Live-Attenuated Porcine Reproductive and Respiratory Syndrome Virus Strain

Viruses ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 817
Author(s):  
Jayeshbhai Chaudhari ◽  
Chia-Sin Liew ◽  
Aspen M. Workman ◽  
Jean-Jack M. Riethoven ◽  
David Steffen ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Lymphoid Tissue ◽  
Innate Immune ◽  
Respiratory Syndrome Virus ◽  
Lymphoid Tissues ◽  
Innate Immune Responses ◽  
Cell Homing ◽  
T Cell Homing ◽  
Prrsv Strain

Both virulent and live-attenuated porcine reproductive and respiratory syndrome virus (PRRSV) strains can establish persistent infection in lymphoid tissues of pigs. To investigate the mechanisms of PRRSV persistence, we performed a transcriptional analysis of inguinal lymphoid tissue collected from pigs experimentally infected with an attenuated PRRSV strain at 46 days post infection. A total of 6404 differentially expressed genes (DEGs) were detected of which 3960 DEGs were upregulated and 2444 DEGs were downregulated. Specifically, genes involved in innate immune responses and chemokines and receptors associated with T-cell homing to lymphoid tissues were down regulated. As a result, homing of virus-specific T-cells to lymphoid tissues seems to be ineffective, evidenced by the lower frequencies of virus-specific T-cell in lymphoid tissue than in peripheral blood. Genes associated with T-cell exhaustion were upregulated. Likewise, genes involved in the anti-apoptotic pathway were upregulated. Collectively, the data suggested that the live-attenuated PRRSV strain establishes a pro-survival microenvironment in lymphoid tissue by suppressing innate immune responses, T-cell homing, and preventing cell apoptosis.

scholarly journals Identification of an IL-4-Inducible Gene Expressed in Differentiating Lymphocytes and Male Germ Cells

1990 ◽  
Vol 1 (1) ◽  
pp. 19-30 ◽  
Author(s):  
Nasrin Nabavi ◽  
Michael J. Grusby ◽  
Patricia W. Finn ◽  
Debra J. Wolgemuth ◽  
Laurie H. Glimcher
Keyword(s):  
Germ Cells ◽  
Fetal Liver ◽  
Interleukin 4 ◽  
Lymphoid Tissues ◽  
Developmentally Regulated ◽  
Male Germ Cells ◽  
F9 Cells ◽  
Normal Spleen ◽  
High Level ◽  
B And T Lymphocytes

Interleukin 4 (IL-4) is a cytokine that is involved in the differentiation of B and T lymphocytes. In this report, we describe the identification of a novel gene, N.52, which was cloned from the murine pre-B cell line R8205 grown in the presence of IL-4 for 48 hr. Although N.52 expression is detectable at low levels in unstimulated R8205 cells, the level of N.52 dramatically increases after only .4 hr exposure to IL-4 and remains at a high .level up to 48 hr. Although N.52 expression is low or absent in normal spleen B and T cells, its expression can be induced by the differentiation signals delivered by LPS in B cells and by Con A in T-cell hybrids. While N.52 mRNA is absent in all highly differentiated organs, it is detectable in stem cell harboring lymphoid tissues such as bone marrow, fetal liver, and thymus. Furthermore, N.52 mRNA is expressed at strikingly high levels in the testis, specifically in differentiating male germ cells. It is induced by differentiation signals triggered by the combination of cyclic AMP and retinoic acid in teratocarcinoma F9 cells. Taken together, these data suggest that N.52 is a developmentally regulated gene whose expression in cells of the immune and reproductive systems may be controlled by stimuli that induce differentiation.

scholarly journals Aging Immune System and Its Correlation With Liability to Severe Lung Complications

2021 ◽  
Vol 9 ◽  
Author(s):  
Yongtao Li ◽  
Chengfei Wang ◽  
Meilian Peng
Keyword(s):  
T Cells ◽  
Immune System ◽  
Immune Responses ◽  
Poor Response ◽  
The Elderly ◽  
Lymphoid Tissues ◽  
Adaptive Immune ◽  
Immune Challenges ◽  
B And T Lymphocytes ◽  
Severe Lung

Aging is considered to be a decline in physical and physiological events that extensively affect the body's immunity, and is linked with deterioration in both innate and adaptive immune responses. The immune system exhibits profound age-associated variations, known as immunosenescence, comprising a significantly low production of B and T lymphocytes in bone marrow and thymus, a decreased function of mature lymphocytes in secondary lymphoid tissues, a decrease in the synthesis of fresh naïve T cells, and reduced activation of T cells. Elderly individuals face a greater risk for many diseases particularly respiratory diseases due to their poor response to immune challenges as vigorously as the young. The current review explored the aging immune system, highlight the mortality rates of severe lung complications, such as pneumonia, COVID-19, asthma, COPD, lung cancer, IPF, and acute lung injury, and their correlation with aging immunity. This study can be helpful in better understanding the pathophysiology of aging, immune responses, and developing new approaches to improve the average age of the elderly population.

scholarly journals Clearance of Chikungunya Virus Infection in Lymphoid Tissues Is Promoted by Treatment with an Agonistic Anti-CD137 Antibody

2019 ◽  
Vol 93 (24) ◽  
Author(s):  
Jun P. Hong ◽  
Mary K. McCarthy ◽  
Bennett J. Davenport ◽  
Thomas E. Morrison ◽  
Michael S. Diamond
Keyword(s):  
Dendritic Cells ◽  
B Cells ◽  
Immune Responses ◽  
Germinal Center ◽  
Lymphoid Tissue ◽  
Lymphoid Tissues ◽  
Follicular Dendritic Cells ◽  
Chikv Infection ◽  
Musculoskeletal Tissues ◽  
Follicular Dendritic

ABSTRACT CD137, a member of the tumor necrosis factor receptor superfamily of cell surface proteins, acts as a costimulatory receptor on T cells, natural killer cells, B cell subsets, and some dendritic cells. Agonistic anti-CD137 monoclonal antibody (MAb) therapy has been combined with other chemotherapeutic agents in human cancer trials. Based on its ability to promote tumor clearance, we hypothesized that anti-CD137 MAb might activate immune responses and resolve chronic viral infections. We evaluated anti-CD137 MAb therapy in a mouse infection model of chikungunya virus (CHIKV), an alphavirus that causes chronic polyarthritis in humans and is associated with reservoirs of CHIKV RNA that are not cleared efficiently by adaptive immune responses. Analysis of viral tropism revealed that CHIKV RNA was present preferentially in splenic B cells and follicular dendritic cells during the persistent phase of infection, and animals lacking B cells did not develop persistent CHIKV infection in lymphoid tissue. Anti-CD137 MAb treatment resulted in T cell-dependent clearance of CHIKV RNA in lymphoid tissue, although this effect was not observed in musculoskeletal tissue. The clearance of CHIKV RNA from lymphoid tissue by anti-CD137 MAb was associated with reductions in the numbers of germinal center B cells and follicular dendritic cells. Similar results were observed with anti-CD137 MAb treatment of mice infected with Mayaro virus, a related arthritogenic alphavirus. Thus, anti-CD137 MAb treatment promotes resolution of chronic alphavirus infection in lymphoid tissues by reducing the numbers of target cells for infection and persistence. IMPORTANCE Although CHIKV causes persistent infection in lymphoid and musculoskeletal tissues in multiple animals, the basis for this is poorly understood, which has hampered pharmacological efforts to promote viral clearance. Here, we evaluated the therapeutic effects on persistent CHIKV infection of an agonistic anti-CD137 MAb that can activate T cell and natural killer cell responses to clear tumors. We show that treatment with anti-CD137 MAb promotes the clearance of persistent alphavirus RNA from lymphoid but not musculoskeletal tissues. This occurs because anti-CD137 MAb-triggered T cells reduce the numbers of target germinal center B cells and follicular dendritic cells, which are the primary reservoirs for CHIKV in the spleen and lymph nodes. Our studies help to elucidate the basis for CHIKV persistence and begin to provide strategies that can clear long-term cellular reservoirs of infection.

scholarly journals A Novel Migration Pathway for Rat Dendritic Cells from the Blood: Hepatic Sinusoids–Lymph Translocation

1997 ◽  
Vol 185 (4) ◽  
pp. 777-784 ◽  
Author(s):  
Shunsuke Kudo ◽  
Kenjiro Matsuno ◽  
Taichi Ezaki ◽  
Michio Ogawa
Keyword(s):  
Dendritic Cells ◽  
Lymph Nodes ◽  
Kupffer Cells ◽  
Lymphoid Tissues ◽  
Proliferating Cells ◽  
High Endothelial Venules ◽  
Regional Lymph Nodes ◽  
Migration Pathway ◽  
Migration Pathways

The migration pathways for dendritic cells (DC) from the blood are not yet completely resolved. In our previous study, a selective recruitment of DC progenitors from the blood to the liver was suggested. To clarify the role of the hepatic sinusoids in the migration of blood DC, relatively immature DC and mature DC were isolated from hepatic and intestinal lymph, and intravenously transferred to allogeneic hosts. It was then possible to detect small numbers of DC within secondary lymphoid tissues either by immunostaining for donor type major histocompatibility complex class I antigen or, at much higher sensitivity, for bromodeoxyuridine incorporated by proliferating cells (mainly T lymphocytes), which responded to the alloantigen presented by the administered DC. The intravenously injected DC accumulated in the paracortex of regional lymph nodes of the liver via a lymph-borne pathway. Intravenously injected fluorochrome-labeled syngeneic DC behaved similarly. In contrast, very few DC were found in spleen sections and were hardly detectable in other lymph nodes or in other tissues. An in situ cell binding assay revealed a significant and selective binding of DC to Kupffer cells in liver cryosections. It is concluded that rat DC can undergo a blood–lymph translocation via the hepatic sinusoids, but not via the high endothelial venules of lymph nodes. Hence the hepatic sinusoids may act as a biological concentrator of blood DC into the regional hepatic nodes. Kupffer cells may play an important role in this mechanism.

scholarly journals L-Selectin Shedding Does Not Regulate Constitutive T Cell Trafficking but Controls the Migration Pathways of Antigen-activated T Lymphocytes

2003 ◽  
Vol 198 (9) ◽  
pp. 1323-1335 ◽  
Author(s):  
Elena Galkina ◽  
Kyriakos Tanousis ◽  
Graham Preece ◽  
Mauro Tolaini ◽  
Dimitris Kioussis ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Mutant Form ◽  
Cell Trafficking ◽  
Lymphocyte Migration ◽  
High Endothelial Venules ◽  
Activated T Cells ◽  
Activated T Lymphocytes ◽  
Migration Pathways

L-Selectin mediates rolling of lymphocytes in high endothelial venules (HEVs) of peripheral lymph nodes (PLNs). Cross-linking of L-selectin causes proteolytic shedding of its ectodomain, the physiological significance of which is unknown. To determine whether L-selectin shedding regulates lymphocyte migration, a mutant form that resists shedding (LΔP-selectin) was engineered. Transgenic mice expressing either LΔP or wild-type (WT) L-selectin on T cells were crossed with L-selectin knockout (KO) mice. The cellularity and subset composition of secondary lymphoid organs did not differ between LΔP and WT mice, however, they were different from C57BL/6. Plasma levels of soluble L-selectin in LΔP mice were reduced to <5% of WT and C57BL/6 mice. The rolling properties of T lymphocytes from LΔP and WT mice on immobilized L-selectin ligands were similar. Furthermore, similar numbers of LΔP and WT T lymphocytes were recruited from the bloodstream into PLNs in mice, although LΔP T cells transmigrated HEVs more slowly. WT, but not LΔP-selectin, underwent rapid, metalloproteinase-dependent shedding after TCR engagement, and LΔP T cells retained the capacity to enter PLNs from the bloodstream. These results suggest that the ability to shed L-selectin is not required for T cell recirculation and homing to PLNs. However, L-selectin shedding from antigen-activated T cells prevents reentry into PLNs.

Sulphated endothelial ligands for L-selectin in lymphocyte homing and inflammation

2003 ◽  
Vol 31 (2) ◽  
pp. 313-317 ◽  
Author(s):  
A. van Zante ◽  
S.D. Rosen
Keyword(s):  
Monoclonal Antibody ◽  
Endothelial Cells ◽  
Lymphoid Tissues ◽  
Lymphocyte Homing ◽  
High Endothelial Venules ◽  
Selectin Ligands ◽  
Peripheral Lymph ◽  
Selectin Ligand ◽  
Endothelial Ligands ◽  
Peripheral Node

Lymphocytes from the blood home to secondary lymphoid tissues through a process of tethering, rolling, firm adhesion and transmigration. Tethering and rolling of lymphocytes is mediated by the interaction of L-selectin on lymphocytes with sulphated ligands expressed by the specialized endothelial cells of high endothelial venules (HEVs). The sulphate-dependent monoclonal antibody MECA79 stains HEVs in peripheral lymph nodes and recognizes the complex of HEV ligands for L-selectin termed peripheral node addressin. High endothelial cell GlcNAc-6-sulphotransferase/L-selectin ligand sulphotransferase is a HEV-expressed sulphotransferase that contributes to the formation of the MECA79 epitope and L-selectin ligands on lymph node HEVs. MECA79-reactive vessels are also common at sites of chronic inflammation, suggesting mechanistic parallels between lymphocyte homing and inflammatory trafficking.

scholarly journals Comparison of a Regulated Delayed Antigen Synthesis System withIn Vivo-Inducible Promoters for Antigen Delivery by Live AttenuatedSalmonellaVaccines

2010 ◽  
Vol 79 (2) ◽  
pp. 937-949 ◽  
Author(s):  
Shifeng Wang ◽  
Yuhua Li ◽  
Huoying Shi ◽  
Wei Sun ◽  
Kenneth L. Roland ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Responses ◽  
Lymphoid Tissues ◽  
Host Immune System ◽  
Antigen Delivery ◽  
Synthesis System ◽  
Inducible Promoters ◽  
Antigen Gene ◽  
High Level

ABSTRACTInduction of strong immune responses against a vectored antigen in hosts immunized with live attenuatedSalmonellavaccines is related in part to the amount of antigen delivered and the overall fitness of theSalmonellavector in relation to its ability to stimulate the host immune system. Constitutive high-level antigen synthesis causes a metabolic burden to the vaccine vector strain that can reduce the vaccine strain's ability to interact with host lymphoid tissues, resulting in a compromised immune response. A solution to this problem is the use of systems that regulate antigen gene expression, permitting high levels of antigen synthesis only after the vaccine strain has reached its target tissues.In vivo-inducible promoters (IVIPs) are often used to accomplish this. We recently developed an alternative strategy, a regulated delayed antigen synthesis (RDAS) system, in which the LacI-repressible Ptrcpromoter controls antigen gene expression by adding arabinose. In this paper, we compared the RDAS system with two commonly used IVIPs, PssaGand PpagC. Three nearly identical plasmids, differing only in the promoter used to direct transcription of the pneumococcalpspAgene, Ptrc, PssaG, or PpagC, were constructed and introduced into isogenicSalmonellavaccine strains with or without arabinose-inducible LacI synthesis. Mice immunized with the RDAS strain developed slightly higher titers of mucosal and serum anti-PspA antibodies than PpagC-immunized mice, while titers in mice immunized with the PssaGstrain were 100-fold lower. Both the RDAS and PpagCstrains conferred similar levels of protection againstStreptococcus pneumoniaechallenge, significantly greater than those for the PssaGstrain or controls. Thus, RDAS provides another choice for inclusion in the live vaccine design to increase immunogenicity.

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