scholarly journals Differential Recruitment of Dendritic Cells Subsets to Lymph Nodes Correlates with a Protective or Permissive T-Cell Response duringLeishmania(Viannia)BraziliensisorLeishmania(Leishmania)AmazonensisInfection

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
A. K. Carvalho ◽  
K. Carvalho ◽  
L. F. D. Passero ◽  
M. G. T. Sousa ◽  
V. L. R. da Matta ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Dendritic Cells ◽  
Lymph Nodes ◽  
T Lymphocyte ◽  
Langerhans Cells ◽  
T Cell Response ◽  
Lymphocyte Response ◽  
Draining Lymph Nodes ◽  
Th1 Immune Response

Leishmania (L.) amazonensis(La) andL. (V.) braziliensis(Lb) are responsible for a large clinical and immunopathological spectrum in human disease; whileLamay be responsible for anergic disease,Lbinfection leads to cellular hypersensitivity. To better understand the dichotomy in the immune response caused by theseLeishmaniaspecies, we evaluated subsets of dendritic cells (DCs) and T lymphocyte in draining lymph nodes during the course ofLaandLbinfection in BALB/c mice. Our results demonstrated a high involvement of DCs inLainfection, which was characterized by the greater accumulation of Langerhans cells (LCs); conversely,Lbinfection led to an increase in dermal DCs (dDCs) throughout the infection. Considering the T lymphocyte response, an increase of effector, activated, and memory CD4+T-cells was observed inLbinfection. Interleukin- (IL-) 4- and IL-10-producing CD4+and CD8+T-cells were present in bothLaandLbinfection; however, interferon- (IFN-)γ-producing CD4+and CD8+T-cells were detected only inLbinfection. The results suggest that duringLbinfection, the dDCs were the predominant subset of DCs that in turn was associated with the development of Th1 immune response; in contrastLainfection was associated with a preferential accumulation of LCs and total blockage of the development of Th1 immune response.

scholarly journals Vaginal Submucosal Dendritic Cells, but Not Langerhans Cells, Induce Protective Th1 Responses to Herpes Simplex Virus-2

2003 ◽  
Vol 197 (2) ◽  
pp. 153-162 ◽  
Author(s):  
Xinyan Zhao ◽  
Eszter Deak ◽  
Kelly Soderberg ◽  
Melissa Linehan ◽  
David Spezzano ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Lymph Nodes ◽  
Cd4 T Cells ◽  
Langerhans Cells ◽  
Vaginal Mucosa ◽  
Simplex Virus ◽  
Draining Lymph Nodes

Herpes simplex virus (HSV) type 2 infection occurs primarily at the genital mucosal surfaces and is a leading cause of ulcerative lesions. Despite the availability of animal models for HSV-2 infection, little is known regarding the mechanism of immune induction within the vaginal mucosa. Here, we examined the cell types responsible for the initiation of protective Th1 immunity to HSV-2. Intravaginal inoculation of HSV-2 led to a rapid recruitment of submucosal dendritic cells (DCs) to the infected epithelium. Subsequently, CD11c+ DCs harboring viral peptides in the context of MHC class II molecules emerged in the draining lymph nodes and were found to be responsible for the stimulation of IFNγ secretion from HSV-specific CD4+ T cells. Other antigen-presenting cells including B cells and macrophages did not present viral peptides to T cells in the draining lymph nodes. Next, we assessed the relative contribution to immune generation by the Langerhans cells in the vaginal epithelium, the submucosal CD11b+ DCs, and the CD8α+ lymph node DCs. Analysis of these DC populations from the draining lymph nodes revealed that only the CD11b+ submucosal DCs, but not Langerhans cell–derived or CD8α+ DCs, presented viral antigens to CD4+ T cells and induced IFNγ secretion. These results demonstrate a previously unanticipated role for submucosal DCs in the generation of protective Th1 immune responses to HSV-2 in the vaginal mucosa, and suggest their importance in immunity to other sexually transmitted diseases.

scholarly journals Using Natural Adjuvants to Stimulate Anti-Tumour Immune Responses

2021 ◽  
Author(s):  
◽  
Sabine Kuhn
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Immune Responses ◽  
Lymph Nodes ◽  
Nk Cells ◽  
Cd8 T Cells ◽  
Tumour Growth ◽  
Tumour Site ◽  
Effector Cells ◽  
Draining Lymph Nodes

<p><b>The anti-tumour immune response is often not potent enough to prevent or eradicate disease. Dendritic cells (DCs) are professional antigen-presenting cells that are critical for the initiation of immune responses. While DCs frequently infiltrate tumours, lack of activation together with immuno-suppressive factors from the tumour can hamper an effective anti-tumour immune response.</b></p> <p>In this thesis, the ability of microbial stimuli and danger signals to overcome suppression and re-programme DCs and macrophages to an immuno-stimulatory phenotype was investigated. Whole live Mycobacterium smegmatis and BCG were used to provide multiple pathogen-associated molecular patterns. The intracellularly-recognised toll-like-receptor (TLR) ligands CpG and Poly IC, as well as the extracelullarly recognised TLR ligand LPS, and the danger signal monosodium-urate crystals (MSU) were also included.</p> <p>Bone-marrow derived DCs were found to respond to all adjuvants in vitro and DCs in tumour cell suspensions could be activated ex vivo. To assess the ability of adjuvants to enhance anti-tumour responses in vivo, immune-competent mice bearing established subcutaneous B16F1 melanomas were injected peri-tumorally with the different adjuvants. In line with previous reports, CpG treatment was effective in delaying tumour growth and increasing survival. A similar effect was found with Poly IC, but not with LPS, M. smegmatis, BCG or MSU alone. Combination of M. smegmatis + MSU, however, significantly delayed tumour growth and prolonged survival, while combinations of MSU + BCG or LPS were ineffective. Similar results were obtained using the B16.OVA melanoma and E.G7-OVA thymoma subcutaneous tumour models. In addition, Poly IC and MSU + M. smegmatis reduced primary tumour growth as well as lung metastases in the orthotopic 4T1 breast carcinoma model.</p> <p>Both Poly IC and MSU + M. smegmatis elicited an anti-tumour immune response that required CD8 T cells as well as NK cells. These treatments also resulted in increased proliferation of CD8 T cells and NK cells in tumour-draining lymph nodes, augmented infiltration of effector cells into the tumour, as well as enhanced production of in ammatory cytokines by effector cells and DCs in tumours. In addition, MSU + M. smegmatis also stimulated CD4 T cell proliferation, tumour-infiltrationand activation, while at the same time decreasing the frequency of regulatory T cells in tumours.</p> <p>Activation of a successful immune response to tumours was associated with early induction of IL-12 and IFNʸ, as well as moderate levels of pro-inflammatory cytokines at the tumour site and systemically. Furthermore, anti-tumour activity correlated with the induction of inflammatory monocyte-derived DCs in tumour-draining lymph nodes. These DCs were also observed in adjuvant treated tumours and their appearance was preceded by accumulation of inflammatory monocytes at the tumour site.</p> <p>These findings suggest that specific natural adjuvants can successfully modify the tumour environment and enhance the innate and adaptive anti-tumour immune response to delay tumour progression and increase survival.</p>

scholarly journals Huaier Extractum Promotes Dendritic Cells Maturation and Favors them to Induce Th1 Immune Response: One of the Mechanisms Underlying Its Anti-Tumor Activity

2020 ◽  
Vol 19 ◽  
pp. 153473542094683
Author(s):  
Jun Pan ◽  
Zhou Jiang ◽  
Dang Wu ◽  
Chenghui Yang ◽  
Zhen Wang ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Dendritic Cells ◽  
Direct Action ◽  
Akt Signaling ◽  
In Vitro Experiments ◽  
4T1 Breast Cancer ◽  
Anti Tumor Activity ◽  
Th1 Immune Response

Huaier, a sandy beige mushroom with anti-tumor effects, has been applied into Traditional Chinese Medicine for more than 1600 years. Previous studies showed that Huaier exerted its anti-tumor effects not only by direct action on tumor cells, but also indirectly by modulation of immune function. In the present study, we found that Huaier treatment significantly repressed tumor growth in mice with 4T1 breast cancer and resulted in significant accumulation of CD4+ T cells and mature dendritic cells (DCs) in the tumor microenvironment. In vitro experiments demonstrated that Huaier treatment promoted both DC2.4 and bone marrow derived DCs (BMDCs) to express costimulatory molecules, enhance production of IL-1β and IL-12p70, while it inhibited their phagocytic activities, suggesting that Huaier treatment promotes maturation of DCs. Furthermore, we found Huaier-treated DCs profoundly stimulated proliferation of alloreactive CD4+ T cells and drove them to differentiate into Th1 subset. Expression of PI3K, Akt, p-Akt, JNK, and p-JNK was up-regulated, while p-p38 MAPK was down-regulated in Huaier-treated BMDCs, suggesting that Huaier promotes maturation of DCs with potent ability to activate Th1 immune response via modulation of MAPK and PI3K/Akt signaling pathways. Our findings provide further evidence for the mechanisms underlying the anti-tumor activity of Huaier.

scholarly journals First Genomic Analysis of Dendritic Cells from Lung and Draining Lymph Nodes in Murine Asthma

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Thomas Tschernig ◽  
Christina Hartwig ◽  
Andreas Jeron ◽  
Quoc Thai Dinh ◽  
Marcus Gereke ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Lymph Nodes ◽  
Lung Tissue ◽  
Cell Sorting ◽  
Allergic Inflammation ◽  
Genomic Analysis ◽  
T Cell Response ◽  
Transcriptional Analysis ◽  
Gene Arrays ◽  
Draining Lymph Nodes

Asthma is the consequence of allergic inflammation in the lung compartments and lung-draining lymph nodes. Dendritic cells initiate and promote T cell response and drive it to immunity or allergy. However, their modes of action during asthma are poorly understood. In this study, an allergic inflammation with ovalbumin was induced in 38 mice versus 42 control animals. After ovalbumin aerosol challenge, conventional dendritic cells (CD11c/MHCII/CD8) were isolated from the lungs and the draining lymph nodes by means of magnetic cell sorting followed by fluorescence-activated cell sorting. A comparative transcriptional analysis was performed using gene arrays. In general, many transcripts are up- and downregulated in the CD8−dendritic cells of the allergic inflamed lung tissue, whereas few genes are regulated in CD8+dendritic cells. The dendritic cells of the lymph nodes also showed minor transcriptional changes. The data support the relevance of the CD8−conventional dendritic cells but do not exclude distinct functions of the small population of CD8+dendritic cells, such as cross presentation of external antigen. So far, this is the first approach performing gene arrays in dendritic cells obtained from lung tissue and lung-draining lymph nodes of asthmatic-like mice.

scholarly journals Motility Dynamics of T Cells in Tumor-Draining Lymph Nodes: A Rational Indicator of Antitumor Response and Immune Checkpoint Blockade

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4616
Author(s):  
Yasuhiro Kanda ◽  
Taku Okazaki ◽  
Tomoya Katakai
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Lymph Nodes ◽  
Cell Motility ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Tumor Immunotherapy ◽  
Checkpoint Blockade ◽  
Draining Lymph Nodes

The migration status of T cells within the densely packed tissue environment of lymph nodes reflects the ongoing activation state of adaptive immune responses. Upon encountering antigen-presenting dendritic cells, actively migrating T cells that are specific to cognate antigens slow down and are eventually arrested on dendritic cells to form immunological synapses. This dynamic transition of T cell motility is a fundamental strategy for the efficient scanning of antigens, followed by obtaining the adequate activation signals. After receiving antigenic stimuli, T cells begin to proliferate, and the expression of immunoregulatory receptors (such as CTLA-4 and PD-1) is induced on their surface. Recent findings have revealed that these ‘immune checkpoint’ molecules control the activation as well as motility of T cells in various situations. Therefore, the outcome of tumor immunotherapy using checkpoint inhibitors is assumed to be closely related to the alteration of T cell motility, particularly in tumor-draining lymph nodes (TDLNs). In this review, we discuss the migration dynamics of T cells during their activation in TDLNs, and the roles of checkpoint molecules in T cell motility, to provide some insight into the effect of tumor immunotherapy via checkpoint blockade, in terms of T cell dynamics and the importance of TDLNs.

scholarly journals De Novo–Induced Self-Antigen–Specific Foxp3+ Regulatory T Cells Impair the Accumulation of Inflammatory Dendritic Cells in Draining Lymph Nodes

2015 ◽  
Vol 194 (12) ◽  
pp. 5812-5824 ◽  
Author(s):  
Themis Alissafi ◽  
Aikaterini Hatzioannou ◽  
Marianna Ioannou ◽  
Tim Sparwasser ◽  
Joachim R. Grün ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Regulatory T Cells ◽  
Lymph Nodes ◽  
De Novo ◽  
Inflammatory Dendritic Cells ◽  
Self Antigen ◽  
Draining Lymph Nodes

scholarly journals Heterologous Prime-Boost Vaccination with a Peptide-Based Vaccine and Viral Vector Reshapes Dendritic Cell, CD4+ and CD8+ T Cell Phenotypes to Improve the Antitumor Therapeutic Effect

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 6107
Author(s):  
Tamara Hofer ◽  
Matteo Rossi ◽  
Susanna Carboni ◽  
Wilma Di Berardino Besson ◽  
Dorothee von Laer ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Lymph Nodes ◽  
Cd8 T Cells ◽  
Cd4 T Cells ◽  
Viral Vector ◽  
Mouse Tumor ◽  
Protein Vaccine ◽  
Boost Vaccination ◽  
Draining Lymph Nodes

Heterologous prime-boost settings with a protein vaccine and the viral vector vesicular stomatitis virus, both expressing tumor-associated antigens (KISIMA-TAA and VSV-GP-TAA), have been previously shown to generate potent antitumor immunity. In the cold TC-1 model (HPV antigen) and the immune-infiltrate MC-38 model (Adpgk, Reps1 and Rpl18 neo-antigens), we further investigated pivotal immune cells that educate CD8+ T cells. Heterologous prime-boost vaccination induced a superior antitumor response characterized by the increase in number and functionality of antigen-specific CD8+ T cells, recruitment of cross-presenting dendritic cells, and polarization of CD4+ T cells towards an antitumor Th1 phenotype within the tumor and tumor-draining lymph nodes, turning the cold TC-1 tumor into a hot, inflamed tumor. In the inflamed MC-38 tumor model, treatment combination markedly prolonged the overall survival of mice. Treatment with multi-epitope vaccines also induced high frequencies of multiple antigen specificities in the periphery and in the tumor. Prime-boost treatment reduced tumor-infiltrating regulatory CD4+ T cells whilst increasing cross-presenting dendritic cells in tumor-draining lymph nodes. In conclusion, heterologous prime-boost vaccination possesses the ability to induce a potent anti-tumor response in both immune-excluded and immune-infiltrated mouse tumor models. Additionally, this study highlights the design of a multi-epitope vaccine for cancer immunotherapy.

scholarly journals Vaccination and Infection of Swine With Salmonella Typhimurium Induces a Systemic and Local Multifunctional CD4+ T-Cell Response

2021 ◽  
Vol 11 ◽  
Author(s):  
Selma Schmidt ◽  
Elena L. Sassu ◽  
Eleni Vatzia ◽  
Alix Pierron ◽  
Julia Lagler ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Lymph Nodes ◽  
T Cell Response ◽  
Effector Memory ◽  
Cell Immune Response ◽  
Control Group ◽  
Tnf Α ◽  
Ifn Γ

The gram-negative facultative intracellular bacteria Salmonella Typhimurium (STM) often leads to subclinical infections in pigs, but can also cause severe enterocolitis in this species. Due to its high zoonotic potential, the pathogen is likewise dangerous for humans. Vaccination with a live attenuated STM strain (Salmoporc) is regarded as an effective method to control STM infections in affected pig herds. However, information on the cellular immune response of swine against STM is still scarce. In this study, we investigated the T-cell immune response in pigs that were vaccinated twice with Salmoporc followed by a challenge infection with a virulent STM strain. Blood- and organ-derived lymphocytes (spleen, tonsils, jejunal and ileocolic lymph nodes, jejunum, ileum) were stimulated in vitro with heat-inactivated STM. Subsequently, CD4+ T cells present in these cell preparations were analyzed for the production of IFN-γ, TNF-α, and IL-17A by flow cytometry and Boolean gating. Highest frequencies of STM-specific cytokine-producing CD4+ T cells were found in lamina propria lymphocytes of jejunum and ileum. Significant differences of the relative abundance of cytokine-producing phenotypes between control group and vaccinated + infected animals were detected in most organs, but dominated in gut and lymph node-residing CD4+ T cells. IL-17A producing CD4+ T cells dominated in gut and gut-draining lymph nodes, whereas IFN-γ/TNF-α co-producing CD4+ T cells were present in all locations. Additionally, the majority of cytokine-producing CD4+ T cells had a CD8α+CD27- phenotype, indicative of a late effector or effector memory stage of differentiation. In summary, we show that Salmonella-specific multifunctional CD4+ T cells exist in vaccinated and infected pigs, dominate in the gut and most likely contribute to protective immunity against STM in the pig.

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