The Function of Local Lymphoid Tissues in Pulmonary Immune Responses

2007 ◽  
pp. 55-68 ◽  
Author(s):  
Juan Moyron-Quiroz ◽  
Javier Rangel-Moreno ◽  
Damian M. Carragher ◽  
Troy D. Randall
Keyword(s):  
Immune Responses ◽  
Lymphoid Tissues

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.

Identification of Chemical Compounds from Artemisia gmelinii using UPLC-QTOF-MS/MS and their Regulatory Effects on Immune Responses in DSS-Induced Colitis Mice

2021 ◽  
pp. 1-23
Author(s):  
Yang-Ju Son ◽  
Ji Min Shin ◽  
In Jin Ha ◽  
Saruul Erdenebileg ◽  
Da Seul Jung ◽  
...  
Keyword(s):  
Immune Responses ◽  
High Performance ◽  
Activity Index ◽  
Disease Activity Index ◽  
Ethanol Extract ◽  
Chemical Compounds ◽  
Chronic Inflammatory Disease ◽  
Lymphoid Tissues ◽  
Food Ingredient ◽  
Cytokines And Chemokines

Artemisia gmelinii Web. ex Stechm. (AG), a popular medicinal herb in Asia, has been used as a common food ingredient in Korea and is traditionally known for its anti-inflammatory properties. Therefore, in this study, we aimed to investigate whether AG relieves IBD, a classic chronic inflammatory disease of the gastrointestinal tract. We identified 35 chemical compounds in AG ethanol extract using ultra-high-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry. In mice with DSS-induced IBD, AG administration attenuated the disease activity index and the serum and colonic levels of inflammatory cytokines and chemokines. AG treatment decreased nuclear factor-[Formula: see text]B (NF-[Formula: see text]B) signaling, a key mediator of inflammation, in the mouse colons. Additionally, AG extract enhanced immune responses in lymphoid tissues such as spleen and Peyer’s patches. Thus, AG consumption potently ameliorated IBD symptoms and improved immune signaling in lymphoid tissues.

scholarly journals Regulatory roles of IL-10–producing human follicular T cells

2019 ◽  
Vol 216 (8) ◽  
pp. 1843-1856 ◽  
Author(s):  
Pablo F. Cañete ◽  
Rebecca A. Sweet ◽  
Paula Gonzalez-Figueroa ◽  
Ilenia Papa ◽  
Naganari Ohkura ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
B Cell ◽  
Foxp3 Expression ◽  
Antibody Responses ◽  
T Cell Proliferation ◽  
Lymphoid Tissues ◽  
Human Tonsil ◽  
Follicular Helper ◽  
Cell Class

Mucosal lymphoid tissues such as human tonsil are colonized by bacteria and exposed to ingested and inhaled antigens, requiring tight regulation of immune responses. Antibody responses are regulated by follicular helper T (TFH) cells and FOXP3+ follicular regulatory T (TFR) cells. Here we describe a subset of human tonsillar follicular T cells identified by expression of TFH markers and CD25 that are the main source of follicular T (TF) cell–derived IL-10. Despite lack of FOXP3 expression, CD25+ TF cells resemble T reg cells in high CTLA4 expression, low IL-2 production, and their ability to repress T cell proliferation. CD25+ TF cell–derived IL-10 dampens induction of B cell class-switching to IgE. In children, circulating total IgE titers were inversely correlated with the frequencies of tonsil CD25+ TF cells and IL-10–producing TF cells but not with total T reg cells, TFR, or IL-10–producing T cells. Thus, CD25+ TF cells emerge as a subset with unique T and B cell regulatory activities that may help prevent atopy.

The Immune Responses and Lymphoid Tissues of Neonatally Thymectomized, X-Irradiated Mice

1970 ◽  
Vol 39 (1) ◽  
pp. 62-81 ◽  
Author(s):  
G. Mosser ◽  
R.A. Good ◽  
M.D. Cooper
Keyword(s):  
Immune Responses ◽  
Lymphoid Tissues

Therapeutic Antimyeloma Effect of Dendritic-Tumor Cells Hybrids Transduced with Adenovirus Encoding CD40L.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1709-1709
Author(s):  
Eva Alvarez ◽  
Esther Moga ◽  
Jorge Sierra ◽  
Javier Briones
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Tumor Cells ◽  
Antitumor Effect ◽  
Tumor Antigens ◽  
Recombinant Adenovirus ◽  
Lymphoid Tissues ◽  
Term Survival ◽  
Mhc Ii

Abstract Dendritic cells (DCs) are the main antigen presenting cells and play a pivotal role in the stimulation of T-cell immune responses. DCs cultured in the presence of a single tumor antigen can elicit an immune response against tumor cells expressing that antigen. However, simultaneous use of several tumor antigens may be advantageous since polyclonal activation of T cells against different tumor antigens may be a better approach to eradicate tumor cells. In this sense, fusions of dendritic and tumor cells (FCs) show a broad spectrum of tumor antigens, both known and unidentified, to be presented by class I and II MHC. Although prophylactic vaccines were successful in murine models, the results in the therapeutic setting have been unsatisfactory. We hypothesised that enhancing costimulation of FCs would help to break tumor tolerance once the tumor is established. To this purpose, we transduced FCs with a recombinant adenovirus encoding CD40L (AdvCD40L or AdvGFP as control) and we studied the therapeutic antitumoral effect of the administration of FC-CD40L in a murine model of myeloma. DCs obtained from day 7-bone marrow cultures of Balb/c mice were fused with tumor cells, a syngeneic murine myeloma cell line (4TOO). FCs hybrids were generated with PEG and selected after culturing in HAT medium plus GM-CSF for 7 days. FC were quantified by determining the percentage of cells that coexpress specific DC (CD11c) and tumor markers (CD138). Mean fusion efficiency was 30% (20–40%) and FCs expressed moderate levels of CD80, CD83, CD86, CD54, CD40 and MHC II and did not express CD40L. FC-CD40L showed a significant increase of expression of costimulatory molecules (CD80, CD86, CD54, and MHC II) compared to FC-GFP (p=0.011). Moreover, in a syngeneic mixed lymphocyte reaction, FC-CD40L induced a two-fold higher T-cell proliferation than FC-GFP or FC alone. In addition, FC-CD40L had improved migration to lymphoid tissues, preferentially to spleen, in comparison with FC-GFP (2.8% versus 1.6%). The antitumor effect of FC-CD40L was analyzed in vivo. Mice (n=10 per group) were injected i.v. with 2.5×105 tumor cells and treated with irradiated FC, FC-GFP or FC-CD40L (1×106 cells each) on days 2, 6 and 10 after tumor challenge. 40% of mice treated with FC-CD40L had long-term survival (>120 days). In contrast, all of mice treated with FC or FC-GFP died between days 25 and 35 (p=0.012). In parallel, treatment with mixed cells (not fused DC+ tumor cells), mix transduced with AdvGFP, or mix transduced with AdvCD40L did not provide any significant antitumor effect. We conclude that FCs transduced with AdvCD40L better stimulate in vitro and in vivo immune responses than FC alone and may provide a new strategy for treating patients with multiple myeloma or lymphoma.

scholarly journals Immunogenicity of a Live Recombinant Salmonellaenterica Serovar Typhimurium Vaccine Expressing pspA in Neonates and Infant Mice Born from Naïve and Immunized Mothers

2010 ◽  
Vol 17 (3) ◽  
pp. 363-371 ◽  
Author(s):  
Huoying Shi ◽  
Shifeng Wang ◽  
Kenneth L. Roland ◽  
Bronwyn M. Gunn ◽  
Roy Curtiss
Keyword(s):  
Immune Responses ◽  
Oral Delivery ◽  
Protective Antigen ◽  
Protective Efficacy ◽  
Maternal Antibodies ◽  
Interleukin 4 ◽  
Lymphoid Tissues ◽  
Adult Mice ◽  
Serovar Typhimurium ◽  
Vectored Vaccine

ABSTRACTWe are developing aSalmonellavectored vaccine to prevent infant pneumonia and other diseases caused byStreptococcus pneumoniae. One prerequisite for achieving this goal is to construct and evaluate new recombinant attenuatedSalmonellavaccine (RASV) strains suitable for use in neonates and infants.Salmonella entericaserovar Typhimurium strain χ9558(pYA4088) specifies delivery of the pneumococcal protective antigen PspA and can protect adult mice from challenge withS. pneumoniae. This strain is completely safe for oral delivery to day-old and infant mice. Here we assess the colonizing ability, immunogenicity, and protective efficacy of χ9558(pYA4088) in neonatal mice. Colonization was assessed in mice 0, 2, 4, or 7 days of age after oral inoculation. In the presence of maternal antibodies, the colonization of lymphoid tissues was delayed, but the immune responses were enhanced in mice born to immunized mothers. Both oral and intranasal routes were used to assess immunogenicity. All orally or intranasally immunized neonatal and infant mice born to either immunized or naïve mothers developed PspA-specific mucosal and systemic immune responses. Mice born to immunized mothers produced higher titers of PspA-specific antibodies in the blood and mucosa and greater numbers of PspA-specific interleukin-4 (IL-4)-secreting cells than mice born to naïve mothers. More importantly, mice born to immune mothers showed a significant increase in protection againstS. pneumoniaechallenge. These results suggest that strain χ9558(pYA4088) can circumvent some of the limitations of the immature immune system in neonatal and infant mice, generating enhanced protective immune responses in the presence of maternal antibodies.

scholarly journals In vivo monitoring of transfected DNA, gene expression kinetics, and cellular immune responses in mice immunized with a human NIS gene-expressing plasmid

2016 ◽  
Vol 29 (4) ◽  
pp. 612-625 ◽  
Author(s):  
Hye-Youn Son ◽  
Yong-Hyun Jeon ◽  
June-Key Chung ◽  
Chul-Woo Kim
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Immune Responses ◽  
Whole Body ◽  
Lymphoid Tissues ◽  
Sequential Presentation ◽  
Sodium Iodide Symporter ◽  
Systemic Injection ◽  
Nis Gene

In assessing the effectiveness of DNA vaccines, it is important to monitor: (1) the kinetics of target gene expression in vivo; and (2) the movement of cells that become transfected with the plasmid DNA used in the immunization of a subject. In this study, we used, as a visual imaging marker, expression of the transfected human sodium/iodide symporter ( hNIS) gene, which enhances intracellular radio-pertechnetate (TcO4–) accumulation. After intradermal (i.d.) and systemic injection of mice with pcDNA-hNIS and radioactive Technetium-99m (Tc-99m), respectively, whole-body images were obtained by nuclear scintigraphy. The migration of mice cells transfected with the hNIS gene was monitored over a 2-week period by gamma-radioactivity counting of isolated cell populations and was demonstrated in peripheral lymphoid tissues, especially in the draining lymph nodes (dLNs). Beginning at 24 h after DNA inoculation and continuing for the 2-week monitoring period, hNIS-expressing cells were observed specifically in the T-cell–rich zones of the paracortical area of the dLNs. Over the same time period, high levels of INF-γ–secreting CD8 T-cells were found in the dLNs of the pcDNA-hNIS immunized mice. Tumor growth was also significantly retarded in the mice that received hNIS DNA immunization followed by inoculation with CT26 colorectal adenocarcinoma cells that had been transfected with the rat NIS gene ( rNIS), which is 93% homologous to the hNIS gene. In conclusion, mouse cells transfected with hNIS DNA after i.d. immunization were found to traffic to the dLNs, and hNIS gene expression in these cells continued for at least 2 weeks post immunization. Furthermore, sequential presentation of NIS DNA to T-cells by migratory antigen presenting cells could induce NIS DNA-specific Th1 immune responses and thus retard the growth of NIS-expressing tumors.

scholarly journals THE LYMPHOID TISSUES AND IMMUNE RESPONSES OF NEONATALLY THYMECTOMIZED MICE BEARING THYMUS TISSUE IN MILLIPORE DIFFUSION CHAMBERS

1964 ◽  
Vol 119 (1) ◽  
pp. 177-194 ◽  
Author(s):  
David Osoba ◽  
J. F. A. P. Miller
Keyword(s):  
Immune Responses ◽  
Intestinal Tract ◽  
Lymphoid Cells ◽  
Lymphoid Tissues ◽  
Lymphoid Follicles ◽  
Diffusion Chambers ◽  
Wasting Syndrome ◽  
Thymus Tissue ◽  
Reticular Cells ◽  
Thymectomized Mice

Neonatally thymectomized mice were implanted intraperitoneally at 7 days of age with Millipore diffusion chambers containing either embryonic or neonatal thymus tissue. Mice which received either empty diffusion chambers or no further treatment following neonatal thymectomy served as controls. In contrast to these controls, most of the mice implanted with thymus-filled chambers gained weight satisfactorily, did not develop a wasting syndrome, and had the capacity to produce serum antibodies in response to sheep erythrocytes and to reject allogeneic skin grafts. Lymphoid follicles were present in the lymph nodes, spleen, and intestinal tract of the implanted mice but most still showed some diminution in the population of lymphocytes in both blood and tissues. Control thymectomized mice had markedly depleted lymphoid tissues and low peripheral blood lymphocyte levels. The tissue recovered after 1 to 2 months from the diffusion chambers showed only epithelial-reticular cells but no lymphoid cells. It is suggested that a humoral factor produced by the thymus epithelial-reticular complex may be responsible for endowing lymphoid cells with immunological competence.

scholarly journals New differentiation pathway for double-negative regulatory T cells that regulates the magnitude of immune responses

Blood ◽  
2006 ◽  
Vol 109 (9) ◽  
pp. 4071-4079 ◽  
Author(s):  
Dong Zhang ◽  
Wei Yang ◽  
Nicolas Degauque ◽  
Yan Tian ◽  
Allison Mikita ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Cell Surface ◽  
Immune Responses ◽  
Lymphoid Tissues ◽  
Double Negative ◽  
Healthy Humans

Abstract Recent studies have demonstrated that in peripheral lymphoid tissues of normal mice and healthy humans, 1% to 5% of αβ T-cell receptor–positive (TCR+) T cells are CD4−CD8− (double-negative [DN]) T cells, capable of down-regulating immune responses. However, the origin and developmental pathway of DN T cells is still not clear. In this study, by monitoring CD4 expression during T-cell proliferation and differentiation, we identified a new differentiation pathway for the conversion of CD4+ T cells to DN regulatory T cells. We showed that the converted DN T cells retained a stable phenotype after restimulation and that furthermore, the disappearance of cell-surface CD4 molecules on converted DN T cells was a result of CD4 gene silencing. The converted DN T cells were resistant to activation-induced cell death (AICD) and expressed a unique set of cell-surface markers and gene profiles. These cells were highly potent in suppressing alloimmune responses both in vitro and in vivo in an antigen-specific manner. Perforin was highly expressed by the converted DN regulatory T cells and played a role in DN T-cell–mediated suppression. Our findings thus identify a new differentiation pathway for DN regulatory T cells and uncover a new intrinsic homeostatic mechanism that regulates the magnitude of immune responses. This pathway provides a novel, cell-based, therapeutic approach for preventing allograft rejection.

1436Overexpression of Cytotoxic T-Lymphocyte Associated Antigen-4 suppresses aortic immunoinflammatory responses and prevents angiotensin II-induced abdominal aortic aneurysm formation in mice

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
H Amin ◽  
N Sasaki ◽  
T Yamashita ◽  
T Mizoguchi ◽  
T Hayashi ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
T Cell ◽  
Angiotensin Ii ◽  
Aortic Aneurysm ◽  
Immune Responses ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Negative Regulator ◽  
Lymphoid Tissues ◽  
Abdominal Aortic

Abstract Aims Vascular inflammation via T-cell-mediated immune responses has been shown to be critically involved in the pathogenesis of abdominal aortic aneurysm (AAA). T-cell coinhibitory molecule cytotoxic T-lymphocyte–associated antigen-4 (CTLA-4) is known to act as a potent negative regulator of immune responses. However, the role of this molecule in the development of AAA remains completely unknown. In the present study, we determined the effects of CTLA-4 overexpression on experimental AAA. Methods and results We continuously infused 12-week-old CTLA-4 transgenic (CTLA-4-Tg)/apolipoprotein E–deficient (Apoe−/−) mice (n=35) or control Apoe−/− mice (n=40) fed a high-cholesterol diet with angiotensin II by implanting osmotic mini-pumps and evaluated the development of AAA. Ninety percent of angiotensin II-infused mice developed AAA, with 50% mortality because of aneurysm rupture. Overexpression of CTLA-4 significantly reduced the incidence (66%), mortality (26%), and diameter (18%) of AAA (incidence: P=0.0104; mortality: P=0.031; diameter: P=0.011). These protective effects were associated with a decreased number of effector CD4+ T cells and the downregulated expression of costimulatory molecules CD80 and CD86, ligands for CTLA-4, on CD11c+ dendritic cells in lymphoid tissues. In addition, by performing in situ zymography of the abdominal aortic aneurysm lesions, we observed a trend toward a decrease in MMP activity in the aneurysmal lesion following overexpression of CTLA-4. Finally, CTLA-4-Tg/Apoe−/− mice had reduced macrophage and CD4+ T cell accumulation and MMP activity in the aneurysmal lesion, leading to attenuated aortic inflammation, preserved vessel integrity, and decreased susceptibility to AAA and aortic rupture. Conclusion Our findings suggest that CTLA-4 protects against AAA by suppressing immunoinflammatory responses and could be an attractive therapeutic target for AAA.

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