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Frontiers in Immunology 2023
Topics: Dendritic Cells; Biology
PubMed: 37234177
DOI: 10.3389/fimmu.2023.1206040 -
Frontiers in Immunology 2022Priming of T cells by antigen presenting cells (APCs) is essential for T cell fate decisions, enabling T cells to migrate to specific tissues to exert their effector... (Review)
Review
Priming of T cells by antigen presenting cells (APCs) is essential for T cell fate decisions, enabling T cells to migrate to specific tissues to exert their effector functions. Previously, these interactions were mainly explored using blood-derived cells or animal models. With great advances in single cell RNA-sequencing techniques enabling analysis of tissue-derived cells, it has become clear that subsets of APCs are responsible for priming and modulating heterogeneous T cell effector responses in different tissues. This composition of APCs and T cells in tissues is essential for maintaining homeostasis and is known to be skewed in infection and inflammation, leading to pathological T cell responses. This review highlights the commonalities and differences of T cell priming and subsequent effector function in multiple barrier tissues such as the skin, intestine and female reproductive tract. Further, we provide an overview of how this process is altered during tissue-specific infections which are known to cause chronic inflammation and how this knowledge could be harnessed to modify T cell responses in barrier tissue.
Topics: Animals; Antigen-Presenting Cells; Cell Communication; Female; Inflammation; RNA; T-Lymphocytes
PubMed: 36248804
DOI: 10.3389/fimmu.2022.984356 -
Nano Letters Oct 2019Activation of T cells by antigen presenting cells (APCs) initiates their proliferation, cytokine production, and killing of infected or cancerous cells. We and others...
Activation of T cells by antigen presenting cells (APCs) initiates their proliferation, cytokine production, and killing of infected or cancerous cells. We and others have shown that T-cell receptors require mechanical forces for triggering, and these forces arise during the interaction of T cells with APCs. Efficient activation of T cells in vitro is necessary for clinical applications. In this paper, we studied the impact of combining mechanical, oscillatory movements provided by an orbital shaker with soft, biocompatible, artificial APCs (aAPCs) of various sizes and amounts of antigen. We showed that these aAPCs allow for testing the strength of signal delivered to T cells, and enabled us to confirm that that absolute amounts of antigen engaged by the T cell are more important for activation than the density of antigen. We also found that when our aAPCs interact with T cells in the context of an oscillatory mechanoenvironment, they roughly double antigenic signal strength, compared to conventional, static culture. Combining these effects, our aAPCs significantly outperformed the commonly used Dynabeads. We finally demonstrated that tuning the signal strength down to a submaximal "sweet spot" allows for robust expansion of induced regulatory T cells. In conclusion, augmenting engineered aAPCs with mechanical forces offers a novel approach for tuning of T-cell activation and differentiation.
Topics: Animals; Antigen-Presenting Cells; Artificial Cells; Biomechanical Phenomena; Cells, Cultured; Humans; Lymphocyte Activation; Mice; Receptors, Antigen, T-Cell; T-Lymphocytes
PubMed: 31478664
DOI: 10.1021/acs.nanolett.9b02252 -
Pathology, Research and Practice May 2022Coronavirus Disease 2019 (COVID-19) is one of the three lethal coronavirus outbreaks in the recent two decades and a serious threat to global health all over the world.... (Review)
Review
Coronavirus Disease 2019 (COVID-19) is one of the three lethal coronavirus outbreaks in the recent two decades and a serious threat to global health all over the world. The principal feature of the COVID-19 infection is the so-called "cytokine storm" exaggerated molecular response to virus distribution, which plays massive tissue and organ injury roles. Immunological treatments, including monoclonal antibodies and vaccines, have been suggested as the main approaches in treating and preventing this disease. Therefore, a proper investigation of the roles of antigen-presenting cells (APCs) in the aforementioned immunological responses appears essential. The present review will provide detailed information about APCs' role in the infection and pathogenesis of SARS-CoV-2 and the effect of monoclonal antibodies in diagnosis and treatment.
Topics: Antibodies, Monoclonal; Antigen-Presenting Cells; COVID-19; Humans; SARS-CoV-2
PubMed: 35338971
DOI: 10.1016/j.prp.2022.153848 -
Molecular Carcinogenesis Feb 2022Presentation of tumor antigens is a critical step in producing a robust antitumor immune response. Classically tumor antigens are thought to be presented to both CD8 and... (Review)
Review
Presentation of tumor antigens is a critical step in producing a robust antitumor immune response. Classically tumor antigens are thought to be presented to both CD8 and CD4 T cells by professional antigen-presenting cells (pAPCs) like dendritic cells using major histocompatibility complexes (MHC) I and II. But recent evidence suggests that in the tumor microenvironment (TME) cells other than pAPCs are capable of presenting tumor antigens on both MHC I and II. The evidence currently available on tumor antigen presentation by epithelial cells, vascular endothelial cells (VECs), fibroblasts, and cancer cells is reviewed herein. We refer to these cell types in the TME as "amateur" APCs (aAPCs). These aAPCs greatly outnumber pAPCs in the TME and could, potentially, play a significant role in priming an antitumor immune response. This new evidence supports a different perspective on antigen presentation and suggests new approaches that can be taken in designing immunotherapies to increase T cell priming.
Topics: Antigen Presentation; Antigen-Presenting Cells; Antigens, Neoplasm; Dendritic Cells; Endothelial Cells; Humans; Tumor Microenvironment
PubMed: 34570920
DOI: 10.1002/mc.23354 -
Frontiers in Immunology 2021Despite significant advances in prevention and treatment of transplant rejection with immunosuppressive medications, we continue to face challenges of long-term graft... (Review)
Review
Despite significant advances in prevention and treatment of transplant rejection with immunosuppressive medications, we continue to face challenges of long-term graft survival, detrimental medication side effects to both the recipient and transplanted organ together with risks for opportunistic infections. Transplantation tolerance has so far only been achieved through hematopoietic chimerism, which carries with it a serious and life-threatening risk of graft versus host disease, along with variability in persistence of chimerism and uncertainty of sustained tolerance. More recently, numerous and studies have explored the therapeutic potential of silent clearance of apoptotic cells which have been well known to aid in maintaining peripheral tolerance to self. Apoptotic cells from a donor not only have the ability of down regulating the immune response, but also are a way of providing donor antigens to recipient antigen-presenting-cells that can then promote donor-specific peripheral tolerance. Herein, we review both laboratory and clinical evidence that support the utility of apoptotic cell-based therapies in prevention and treatment of graft host disease and transplant rejection along with induction of donor-specific tolerance in solid organ transplantation. We have highlighted the potential limitations and challenges of this apoptotic donor cell-based therapy together with ongoing advancements and attempts made to overcome them.
Topics: Animals; Antigen-Presenting Cells; Apoptosis; Cell- and Tissue-Based Therapy; Chimerism; Graft Rejection; Graft vs Host Disease; Humans; Immunosuppressive Agents; Organ Transplantation; Tissue Donors; Transplantation Immunology; Transplantation Tolerance; Ureohydrolases
PubMed: 33717145
DOI: 10.3389/fimmu.2021.626840 -
Transplant International : Official... Aug 2017This article provides a transparent description of Mreg_UKR cell products, including manufacture and quality-control processes, using the structure and vocabulary of the... (Review)
Review
This article provides a transparent description of Mreg_UKR cell products, including manufacture and quality-control processes, using the structure and vocabulary of the 'Minimum Information about Tolerogenic Antigen-presenting Cells' reporting guidelines. This information is intended as a resource for those in the field, as well as a stimulus to develop a new wave of immunoregulatory and tissue-reparative monocyte-derived cell therapies.
Topics: Antigen-Presenting Cells; Blood Component Removal; Cell Culture Techniques; Cell Differentiation; Cell Separation; Cell- and Tissue-Based Therapy; Humans; Immunosuppression Therapy; Kidney Transplantation; Living Donors; Macrophages; Monocytes; Transplantation Immunology; Transplantation Tolerance
PubMed: 28543878
DOI: 10.1111/tri.12988 -
Glycobiology Mar 2022Polysaccharide A (PSA) is the immunodominant capsular carbohydrate from the gram negative commensal microbe Bacteroides fragilis that has shown remarkable potency in...
Polysaccharide A (PSA) is the immunodominant capsular carbohydrate from the gram negative commensal microbe Bacteroides fragilis that has shown remarkable potency in ameliorating many rodent models of inflammatory disease by eliciting downstream suppressive CD4+ T cells. PSA is composed of a zwitterionic repeating unit that allows it to be processed by antigen presenting cells (APCs) and presented by MHCII in a glycosylation-dependent manner. While previous work has uncovered much about the interactions between MHCII and PSA, as well as the downstream T cell response, little is known about how PSA affects the phenotype of MHCII+ APCs, including macrophages. Here, we utilized an unbiased systems approach consisting of RNAseq transcriptomics, high-throughput flow cytometry, Luminex analysis and targeted validation experiments to characterize the impact of PSA-mediated stimulation of splenic MHCII+ cells. The data revealed that PSA potently elicited the upregulation of an alternatively activated M2 macrophage transcriptomic and cell surface signature. Cell-type-specific validation experiments further demonstrated that PSA-exposed bone marrow-derived macrophages (BMDMs) induced cell surface and intracellular markers associated with M2 macrophages compared with conventional peptide ovalbumin (ova)-exposed BMDMs. In contrast to macrophages, we also found that CD11c+ dendritic cells (DCs) upregulated the pro-T cell activation costimulatory molecule CD86 following PSA stimulation. Consistent with the divergent BMDM and DC changes, PSA-exposed DCs elicited an antigen-experienced T cell phenotype in co-cultures, whereas macrophages did not. These findings collectively demonstrate that the PSA-induced immune response is characterized by both T cell stimulation via presentation by DCs, and a previously unrecognized anti-inflammatory polarization of macrophages.
Topics: Animals; Anti-Inflammatory Agents; Antigen-Presenting Cells; Dendritic Cells; Humans; Macrophages; Male; Mice; Mice, Inbred C57BL; Polysaccharides; Prostate-Specific Antigen
PubMed: 34939104
DOI: 10.1093/glycob/cwab111 -
Immunological Reviews Jan 2014Adoptive T-cell therapy, where anti-tumor T cells are first prepared in vitro, is attractive since it facilitates the delivery of essential signals to selected subsets... (Review)
Review
Adoptive T-cell therapy, where anti-tumor T cells are first prepared in vitro, is attractive since it facilitates the delivery of essential signals to selected subsets of anti-tumor T cells without unfavorable immunoregulatory issues that exist in tumor-bearing hosts. Recent clinical trials have demonstrated that anti-tumor adoptive T-cell therapy, i.e. infusion of tumor-specific T cells, can induce clinically relevant and sustained responses in patients with advanced cancer. The goal of adoptive cell therapy is to establish anti-tumor immunologic memory, which can result in life-long rejection of tumor cells in patients. To achieve this goal, during the process of in vitro expansion, T-cell grafts used in adoptive T-cell therapy must be appropriately educated and equipped with the capacity to accomplish multiple, essential tasks. Adoptively transferred T cells must be endowed, prior to infusion, with the ability to efficiently engraft, expand, persist, and traffic to tumor in vivo. As a strategy to consistently generate T-cell grafts with these capabilities, artificial antigen-presenting cells have been developed to deliver the proper signals necessary to T cells to enable optimal adoptive cell therapy.
Topics: Animals; Antigen-Presenting Cells; Cell Culture Techniques; Clinical Trials as Topic; Combined Modality Therapy; Cytokines; Genetic Engineering; Humans; Immunologic Memory; Immunotherapy, Adoptive; K562 Cells; Killer Cells, Natural; Neoplasms; Phenotype; Receptors, Antigen, T-Cell; Recombinant Fusion Proteins; T-Lymphocyte Subsets
PubMed: 24329798
DOI: 10.1111/imr.12129 -
Journal of Immunology Research 2019Mesangial cells play a prominent role in the development of inflammatory diseases and autoimmune disorders of the kidney. Mesangial cells perform the essential functions...
BACKGROUND
Mesangial cells play a prominent role in the development of inflammatory diseases and autoimmune disorders of the kidney. Mesangial cells perform the essential functions of helping to ensure that the glomerular structure is stable and regulating capillary flow, and activated mesangial cells acquire proinflammatory activities. We investigated whether activated mesangial cells display immune properties and control the development of T cell immunity.
METHODS
Flow cytometry analysis was used to study the expression of antigen-presenting cell surface markers and costimulatory molecules in mesangial cells. CD4+ T cell activation induced by mesangial cells was detected in terms of T cell proliferation and cytokine production.
RESULTS
IFN--treated mesangial cells express membrane proteins involved in antigen presentation and T cell activation, including MHC-II, ICAM-1, CD40, and CD80. This finding suggests that activated mesangial cells can take up and present antigenic peptides to initiate CD4+ T cell responses and thus act as nonprofessional antigen-presenting cells. Polarization of naïve CD4+ T cells (Th0 cells) towards the Th1 phenotype was induced by coculture with activated mesangial cells, and the resulting Th1 cells showed increased mRNA and protein expression of inflammation-associated genes.
CONCLUSION
Mesangial cells can present antigen and modulate CD4+ T lymphocyte proliferation and differentiation. Interactions between mesangial cells and T cells are essential for sustaining the inflammatory response in a variety of glomerulonephritides. Therefore, mesangial cells might participate in immune function in the kidney.
Topics: Animals; Antigen Presentation; Antigen-Presenting Cells; CD4-Positive T-Lymphocytes; Cells, Cultured; Histocompatibility Antigens Class II; Humans; Interferon-gamma; Kidney Diseases; Lymphocyte Activation; Mesangial Cells; Mice; Mice, Inbred C57BL; Mice, Transgenic; Th1 Cells
PubMed: 31317046
DOI: 10.1155/2019/2121849