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Journal of Immunology Research 2015The protein kinases C (PKCs) are a family of serine/threonine kinases involved in regulating multiple essential cellular processes such as survival, proliferation, and... (Review)
Review
The protein kinases C (PKCs) are a family of serine/threonine kinases involved in regulating multiple essential cellular processes such as survival, proliferation, and differentiation. Of particular interest is the novel, calcium-independent PKCθ which plays a central role in immune responses. PKCθ shares structural similarities with other PKC family members, mainly consisting of an N-terminal regulatory domain and a C-terminal catalytic domain tethered by a hinge region. This isozyme, however, is unique in that it translocates to the immunological synapse between a T cell and an antigen-presenting cell (APC) upon T cell receptor-peptide MHC recognition. Thereafter, PKCθ interacts physically and functionally with downstream effectors to mediate T cell activation and differentiation, subsequently leading to inflammation. PKCθ-specific perturbations have been identified in several diseases, most notably autoimmune disorders, and hence the modulation of its activity presents an attractive therapeutic intervention. To that end, many inhibitors of PKCs and PKCθ have been developed and tested in preclinical and clinical studies. And although selectivity remains a challenge, results are promising for the future development of effective PKCθ inhibitors that would greatly advance the treatment of several T-cell mediated diseases.
Topics: Animals; Antigen-Presenting Cells; Autoimmune Diseases; Humans; Inflammation; Isoenzymes; Protein Kinase C; Receptors, Antigen, T-Cell; T-Lymphocytes
PubMed: 26090489
DOI: 10.1155/2015/348798 -
Frontiers in Immunology 2022Organized intestinal mucosal immune response appears to be restricted to tetrapods. In teleost fish, there is no evidence for the existence of a particular intestinal...
Organized intestinal mucosal immune response appears to be restricted to tetrapods. In teleost fish, there is no evidence for the existence of a particular intestinal region that facilitates the interaction of antigen-presenting cells (APCs) and T cells, such as secondary lymphoid organs. Indeed, despite their importance in the defense against pathogens, the location and manner of APC-T cell interaction within the fish gut is unknown. Here, using non-invasive live imaging of newly developed transgenic reporter lines, we addressed the spatial organization and behavior of APCs and T cells in the intestine of medaka fish both during homeostasis and inflammation. We report that Ccr9a T cells are recruited to a band in the lamina propria next to the muscularis mucosa in which Ccl25-expressing cells are present. Ccr9a T cells contact APCs for several minutes, in a process mediated by connexin 43. This type of interaction was observed in homeostasis and inflammation, with the interaction being longer and more frequent during inflammation. Thus, our results demonstrate that the mucosal immune response in the intestine of medaka is organized and endowed with a specific region with specialized microenvironment and function.
Topics: Animals; Antigen-Presenting Cells; Chemokines, CC; Intestinal Mucosa; Oryzias; Receptors, CCR; T-Lymphocytes
PubMed: 35185906
DOI: 10.3389/fimmu.2022.812899 -
Human Vaccines & Immunotherapeutics Jul 2013Fusions of antigen presenting cells and tumor cells have been investigated in animal models and phase I/II clinical trials as candidate cancer vaccines. In animal... (Review)
Review
Fusions of antigen presenting cells and tumor cells have been investigated in animal models and phase I/II clinical trials as candidate cancer vaccines. In animal studies there have been numerous reports of induction of protective immunity against a wide range of tumor types. Results of clinical trials have been less dramatic, but tumor-specific immune responses have been reported in many patients, with clinical responses to the vaccination in a subset. In this commentary article, I review the current status of antigen presenting cell/tumor cell fusion vaccines for cancer immunotherapy.
Topics: Animals; Antigen-Presenting Cells; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cancer Vaccines; Cell Fusion; Cell- and Tissue-Based Therapy; Humans; Hybrid Cells; Immunotherapy; Lymphocyte Activation; Mice; Neoplasms
PubMed: 23475129
DOI: 10.4161/hv.24235 -
Molecular Immunology Jun 2018Exciting developments in cancer nanomedicine include the engineering of nanocarriers to deliver drugs locally to tumors, increasing efficacy and reducing off-target... (Review)
Review
Exciting developments in cancer nanomedicine include the engineering of nanocarriers to deliver drugs locally to tumors, increasing efficacy and reducing off-target toxicity associated with chemotherapies. Despite nanocarrier advances, metastatic cancer remains challenging to treat due to barriers that prevent nanoparticles from gaining access to remote, dispersed, and poorly vascularized metastatic tumors. Instead of relying on nanoparticles to directly destroy every tumor cell, immunotherapeutic approaches target immune cells to train them to recognize and destroy tumor cells, which, due to the amplification and specificity of an adaptive immune response, may be a more effective approach to treating metastatic cancer. One novel technology for cancer immunotherapy is the artificial antigen presenting cell (aAPC), a micro- or nanoparticle-based system that mimics an antigen presenting cell by presenting important signal proteins to T cells to activate them against cancer. Signal 1 molecules target the T cell receptor and facilitate antigen recognition by T cells, signal 2 molecules provide costimulation essential for T cell activation, and signal 3 consists of secreted cues that further stimulate T cells. Classic microscale aAPCs present signal 1 and 2 molecules on their surface, and biodegradable polymeric aAPCs offer the additional capability of releasing signal 3 cytokines and costimulatory molecules that modulate the T cell response. Although particles of approximately 5-10 μm in diameter may be considered the optimal size of an aAPC for ex vivo cellular expansion, nanoscale aAPCs have demonstrated superior in vivo pharmacokinetic properties and are more suitable for systemic injection. As sufficient surface contact between T cells and aAPCs is essential for activation, nano-aAPCs with microscale contact surface areas have been created through engineering approaches such as shape manipulation and nanoparticle clustering. These design strategies have demonstrated greatly enhanced efficacy of nano-aAPCs, endowing nano-aAPCs with the potential to be among the next generation of cancer nanomedicines.
Topics: Animals; Antigen-Presenting Cells; Artificial Cells; Biomimetics; Humans; Immunotherapy; Magnetite Nanoparticles; Mice; Nanomedicine; Nanoparticles; Nanotechnology; Neoplasms; Particle Size
PubMed: 29525074
DOI: 10.1016/j.molimm.2018.02.016 -
The European Respiratory Journal Jan 2010It is likely that multiple genes contribute to immunoglobulin (Ig)E production. Co-stimulatory molecules are crucial for the cross-talk between antigen presenting cells...
It is likely that multiple genes contribute to immunoglobulin (Ig)E production. Co-stimulatory molecules are crucial for the cross-talk between antigen presenting cells and T-lymphocytes which drives the IgE response. We evaluated gene-gene interactions of haplotype tagging polymorphisms in a pathway of 24 co-stimulatory genes in relation to serum IgE levels. We assessed this at ages 1-2 yrs and 6-8 yrs in 3,062 Dutch children from a pooled data set of three birth cohorts: PIAMA (Prevention and Incidence Asthma and Mite Allergy), PREVASC (Prevention of Asthma in Children) and KOALA (Child, parents and health: lifestyle and genetic constitution). Single- and multi-locus associations with serum IgE levels (3rd versus 1st tertile) were evaluated by Chi-squared tests and the multifactor dimensionality reduction (MDR) method in the following co-stimulatory genes: VTCN1, TNFRSF4, TNFRSF18, TNFRSF14, TNFSF18, TNFSF4, CD28, CTLA4, ICOS, PDCD1, BTLA, CD80, CD86, HLA-G, CD274, PDCD1LG2, CD276, LILRA4, LILRB1, LILRB2, LILRB4, CD40, ICOSLG, and CD40LG. We found multiple statistically significant single-locus ((S)) and multi-locus ((M)) associations for the genes VTCN1(SM), TNFSF18(SM), TNFSF4(S), CD28(S), CTLA4(M), ICOS(S), BTLA(M), CD80(M), CD86(SM), CD274(SM), PDCD1LG2(M), LILRA4(SM), LILRB4(M), and CD40(SM) with serum IgE. Two-locus interactions of CD86 with VTCN1 and CD274 with LILRA4 were confirmed by logistic regression. In conclusion, serum IgE levels are regulated by multiple gene-gene interaction effects in the co-stimulatory pathway. We suggest using research strategies that model multiple gene-gene interactions in genetic studies.
Topics: Antigen-Presenting Cells; Cell Communication; Child; Child, Preschool; Female; Gene Expression Regulation; Humans; Immunoglobulin E; Infant; Male; Prospective Studies; T-Lymphocytes
PubMed: 19574333
DOI: 10.1183/09031936.00018909 -
Virology Journal Dec 2019Porcine circovirus (PCV) disease caused by PCV type 2 (PCV2) is mainly attributed to immunosuppression and immune damage. PCV2 can infect vascular endothelial cells and...
BACKGROUND
Porcine circovirus (PCV) disease caused by PCV type 2 (PCV2) is mainly attributed to immunosuppression and immune damage. PCV2 can infect vascular endothelial cells and induce high expression of endothelial IL-8. Dendritic cells (DCs), as professional antigen-presenting cells, can not only present antigens but also activate naïve T-cells, causing an immune response.
METHODS
To demonstrate whether endothelial IL-8 is the main factor inhibiting the maturation and related functions of dendritic cells during PCV2 infection, monocyte-derived DCs (MoDCs) and porcine iliac artery endothelial cells (PIECs) processed by different methods were co-cultured in two ways. Flow cytometry, molecular probe labeling, fluorescence quantitative PCR, and the MTS assay were used to detect the changes in related functions and molecules of MoDCs.
RESULTS
Compared to those in the PIEC-DC group, the endothelial IL-8 upregulation co-culture group showed significantly lower double-positive rates for CD80/86 and MHC-II of MoDCs and significantly increased endocytosis of MoDCs. Meanwhile, the adhesion rate and average fluorescence intensity of MoDCs were significantly downregulated in migration and adhesion experiments. Furthermore, the MHC-I and LAMP7 mRNA levels in MoDCs and the proliferation of MoDC-stimulated T-cells were markedly reduced. However, the changes in MoDCs of the endothelial IL-8 downregulation co-culture group were the opposite.
CONCLUSIONS
PCV2-induced endothelial IL-8 reduces the adhesion and migration ability of MoDCs, resulting in a decreased maturation rate of MoDCs, and further inhibits antigen presentation by DCs. These results may explain the immunosuppressive mechanism of PCV2 from the perspective of the interaction between endothelial cells and DCs in vitro.
Topics: Animals; Antigen-Presenting Cells; Cell Differentiation; Cells, Cultured; Circovirus; Coculture Techniques; Dendritic Cells; Endothelial Cells; Immunologic Factors; Interleukin-8; Swine
PubMed: 31831027
DOI: 10.1186/s12985-019-1256-z -
Journal of Interferon & Cytokine... Nov 2012Natural killer T (NKT) cells constitute an important subset of T cells that can both directly and indirectly mediate antitumor immunity. However, we and others have... (Review)
Review
Natural killer T (NKT) cells constitute an important subset of T cells that can both directly and indirectly mediate antitumor immunity. However, we and others have reported that cancer patients have a reduction in both NKT cell number and function. NKT cells can be stimulated and expanded with α-GalCer and cytokines and these expanded NKT cells retain their phenotype, remain responsive to antigenic stimulation, and display cytotoxic function against tumor cell lines. These data strongly favor the use of ex vivo expanded NKT cells in adoptive immunotherapy. NKT cell based-immunotherapy has been limited by the use of autologous antigen-presenting cells, which can vary substantially in their quantity and quality. A standardized system that relies on artificial antigen-presenting cells (aAPCs) could produce the stimulating effects of dendritic cell (DC) without the pitfalls of allo- or xenogeneic cells. In this review, we discuss the progress that has been made using CD1d-based aAPC and how this acellular antigen presenting system can be used in the future to enhance our understanding of NKT cell biology and to develop NKT cell-specific adoptive immunotherapeutic strategies.
Topics: Antigen Presentation; Antigen-Presenting Cells; Antigens, CD1d; Cell Line, Tumor; Cytokines; Galactosylceramides; Humans; Immunotherapy, Adoptive; Lymphocyte Activation; Lymphocyte Count; Natural Killer T-Cells; Neoplasms
PubMed: 23050947
DOI: 10.1089/jir.2012.0045 -
Frontiers in Immunology 2021Childhood vaccines have been the cornerstone tool of public health over the past century. A major barrier to neonatal vaccination is the "immaturity" of the infant... (Review)
Review
Childhood vaccines have been the cornerstone tool of public health over the past century. A major barrier to neonatal vaccination is the "immaturity" of the infant immune system and the inefficiency of conventional vaccine approaches at inducing immunity at birth. While much of the literature on fetal and neonatal immunity has focused on the early life propensity toward immune tolerance, recent studies indicate that the fetus is more immunologically capable than previously thought, and can, in some circumstances, mount adaptive B and T cell responses to perinatal pathogens . Although significant hurdles remain before these findings can be translated into vaccines and other protective strategies, they should lend optimism to the prospect that neonatal and even fetal vaccination is achievable. Next steps toward this goal should include efforts to define the conditions for optimal stimulation of infant immune responses, including antigen timing, dose, and route of delivery, as well as antigen presentation pathways and co-stimulatory requirements. A better understanding of these factors will enable optimal deployment of vaccines against malaria and other pathogens to protect infants during their period of greatest vulnerability.
Topics: Adaptive Immunity; Age Factors; Antibodies, Protozoan; Antigen-Presenting Cells; Female; Fetus; Humans; Immune Tolerance; Immunity, Innate; Immunization Schedule; Immunocompetence; Infant, Newborn; Lymphocytes; Malaria; Malaria Vaccines; Maternal-Fetal Exchange; Pregnancy; Vaccination
PubMed: 33679787
DOI: 10.3389/fimmu.2021.634749 -
Frontiers in Immunology 2020Chondroitin sulfate (CS), a type of glycosaminoglycan (GAG), is a linear acidic polysaccharide comprised of repeating disaccharides, modified with sulfate groups at... (Review)
Review
Chondroitin sulfate (CS), a type of glycosaminoglycan (GAG), is a linear acidic polysaccharide comprised of repeating disaccharides, modified with sulfate groups at various positions. Except for hyaluronan (HA), GAGs are covalently bound to core proteins, forming proteoglycans (PGs). With highly negative charges, GAGs interact with a variety of physiologically active molecules, including cytokines, chemokines, and growth factors, and control cell behavior during development and in the progression of diseases, including cancer, infections, and inflammation. Heparan sulfate (HS), another type of GAG, and HA are well reported as regulators for leukocyte migration at sites of inflammation. There have been many reports on the regulation of immune cell function by HS and HA; however, regulation of immune cells by CS has not yet been fully understood. This article focuses on the regulatory function of CS in antigen-presenting cells, including macrophages and dendritic cells, and refers to CSPGs, such as versican and biglycan, and the cell surface proteoglycan, syndecan.
Topics: Adaptive Immunity; Antigen-Presenting Cells; Biglycan; Carbohydrate Conformation; Carbohydrate Sequence; Chondroitin Sulfate Proteoglycans; Chondroitin Sulfates; Dendritic Cells; Humans; Hyaluronan Receptors; Immunity, Innate; Macrophages; Receptor-Like Protein Tyrosine Phosphatases, Class 2; Structure-Activity Relationship; Syndecans; Toll-Like Receptors; Versicans
PubMed: 32194548
DOI: 10.3389/fimmu.2020.00232 -
Frontiers in Bioscience (Landmark... Jan 2011T cells tend to acquire a variety of cell surface molecules derived from antigen presenting cells (APCs). The molecule uptake occurs mainly during direct T/APC contact... (Review)
Review
T cells tend to acquire a variety of cell surface molecules derived from antigen presenting cells (APCs). The molecule uptake occurs mainly during direct T/APC contact and is instigated by specific receptor/ligand interactions, such as T cell receptor (TCR) with a cognate peptide/MHC complex (pMHC) or CD28 with B7. The acquired molecules are targeted for internalization and degradation in the lysosome. Nevertheless, those molecules are expressed on the surface of T cells for a period of time. The presentation of APC-derived ligands by T cells exhibited a multitude of immunological effects via antigen-specific T/T interaction upon recognition of the absorbed antigens by contact with other T cells. Ligand uptake also occurs via absorption of membrane vesicles shed from APCs prior to contact (e.g., exosomes and plasma membrane-derived vesicles). As in ligand absorption via direct T/APC interaction, the absorption of pre-formed membrane vesicles is also dependent on specific receptor/ligand interactions. In this review, biological mechanisms underlying the ligand absorption process as well as the biological significance and application of the event will be discussed.
Topics: Absorption; Animals; Antigen-Presenting Cells; Exosomes; Humans; Ligands; Lymphocyte Activation; Mice; Receptors, Antigen, T-Cell; T-Lymphocytes
PubMed: 21196178
DOI: 10.2741/3695