10 results on '"Andrew G. Soerens"'
Search Results
2. Depleting CD103+ resident memory T cells in vivo reveals immunostimulatory functions in oral mucosa
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J. Michael Stolley, Milcah C. Scott, Vineet Joag, Alexander J. Dale, Timothy S. Johnston, Flavia Saavedra, Noah V. Gavil, Sahar Lotfi-Emran, Andrew G. Soerens, Eyob Weyu, Mark J. Pierson, Mark C. Herzberg, Nu Zhang, Vaiva Vezys, and David Masopust
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Immunology ,Immunology and Allergy - Abstract
The oral mucosa is a frontline for microbial exposure and juxtaposes several unique tissues and mechanical structures. Based on parabiotic surgery of mice receiving systemic viral infections or co-housing with microbially diverse pet shop mice, we report that the oral mucosa harbors CD8+ CD103+ resident memory T cells (TRM), which locally survey tissues without recirculating. Oral antigen re-encounter during the effector phase of immune responses potentiated TRM establishment within tongue, gums, palate, and cheek. Upon reactivation, oral TRM triggered changes in somatosensory and innate immune gene expression. We developed in vivo methods for depleting CD103+ TRM while sparing CD103neg TRM and recirculating cells. This revealed that CD103+ TRM were responsible for inducing local gene expression changes. Oral TRM putatively protected against local viral infection. This study provides methods for generating, assessing, and in vivo depleting oral TRM, documents their distribution throughout the oral mucosa, and provides evidence that TRM confer protection and trigger responses in oral physiology and innate immunity.
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- 2023
3. Cutting Edge: Nucleocapsid Vaccine Elicits Spike-Independent SARS-CoV-2 Protective Immunity
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Vineet Joag, Stephen D O'Flanagan, Joshua M. Thiede, Clare F. Quarnstrom, Clayton K. Mickelson, Marc K. Jenkins, J. Michael Stolley, William E. Matchett, Tyler D. Bold, David Masopust, Michelle N Vu, Vaiva Vezys, Frances K. Shepherd, Vineet D. Menachery, Jennifer A Walter, Samuel Becker, Sathi Wijeyesinghe, Ryan A. Langlois, Eyob Weyu, and Andrew G. Soerens
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Male ,COVID-19 Vaccines ,viruses ,T cell ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Immunology ,Biology ,CD8-Positive T-Lymphocytes ,Antibodies, Viral ,Epitope ,Article ,Cell Line ,Mice ,Immunity ,Cricetinae ,Pandemic ,Chlorocebus aethiops ,medicine ,Immunology and Allergy ,Animals ,Coronavirus Nucleocapsid Proteins ,Vector (molecular biology) ,Lymphocyte Count ,Vero Cells ,SARS-CoV-2 ,Vaccination ,COVID-19 ,Phosphoproteins ,Virology ,Antibodies, Neutralizing ,Mice, Inbred C57BL ,medicine.anatomical_structure ,biology.protein ,Female ,Antibody ,Viral load ,Immunologic Memory - Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the COVID-19 pandemic. Neutralizing Abs target the receptor binding domain of the spike (S) protein, a focus of successful vaccine efforts. Concerns have arisen that S-specific vaccine immunity may fail to neutralize emerging variants. We show that vaccination with a human adenovirus type 5 vector expressing the SARS-CoV-2 nucleocapsid (N) protein can establish protective immunity, defined by reduced weight loss and viral load, in both Syrian hamsters and K18-hACE2 mice. Challenge of vaccinated mice was associated with rapid N-specific T cell recall responses in the respiratory mucosa. This study supports the rationale for including additional viral Ags in SARS-CoV-2 vaccines, even if they are not a target of neutralizing Abs, to broaden epitope coverage and immune effector mechanisms.
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- 2021
4. Tissue-Resident T Cells and Other Resident Leukocytes
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David Masopust and Andrew G. Soerens
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CD4-Positive T-Lymphocytes ,medicine.medical_specialty ,Immunology ,CD8-Positive T-Lymphocytes ,Biology ,Article ,Immune system ,Medical microbiology ,Cell Movement ,Immunity ,Leukocytes ,medicine ,Animals ,Humans ,Immunology and Allergy ,book ,B-Lymphocytes ,Macrophages ,Venous blood ,Immunity, Innate ,Killer Cells, Natural ,medicine.anatomical_structure ,Organ Specificity ,Pediatric Infectious Disease ,book.journal ,Immunologic Memory ,Memory T cell - Abstract
Resident memory T (Trm) cells stably occupy tissues and cannot be sampled in superficial venous blood. Trm cells are heterogeneous but collectively constitute the most abundant memory T cell subset. Trm cells form an integral part of the immune sensing network, monitor for local perturbations in homeostasis throughout the body, participate in protection from infection and cancer, and likely promote autoimmunity, allergy, and inflammatory diseases and impede successful transplantation. Thus Trm cells are major candidates for therapeutic manipulation. Here we review CD8+ and CD4+ Trm ontogeny, maintenance, function, and distribution within lymphoid and nonlymphoid tissues and strategies for their study. We briefly discuss other resident leukocyte populations, including innate lymphoid cells, macrophages, natural killer and natural killer T cells, nonclassical T cells, and memory B cells. Lastly, we highlight major gaps in knowledge and propose ways in which a deeper understanding could result in new methods to prevent or treat diverse human diseases.
- Published
- 2019
5. Cutting Edge: Mouse SARS-CoV-2 Epitope Reveals Infection and Vaccine-Elicited CD8 T Cell Responses
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J. Michael Stolley, Peter J. Southern, Siddheshvar Bhela, Thamotharampillai Dileepan, Maxim C.-J. Cheeran, Vineet Joag, Marc K. Jenkins, Sathi Wijeyesinghe, Joshua M. Thiede, Luca Schifanella, Jules A. Sangala, Clare F. Quarnstrom, Geoffrey T. Hart, Stephen D O'Flanagan, Sung-Wook Hong, Venkatramana D. Krishna, William E. Matchett, Noah V. Gavil, David Masopust, Sailaja Gangadhara, Tyler D. Bold, Eyob Weyu, Ryan A. Langlois, Vaiva Vezys, Rama Rao Amara, and Andrew G. Soerens
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COVID-19 Vaccines ,T cell ,viruses ,Immunology ,Genetic Vectors ,Heterologous ,Epitopes, T-Lymphocyte ,Mice, Transgenic ,Biology ,CD8-Positive T-Lymphocytes ,Epitope ,Article ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Immunity ,HLA-A2 Antigen ,medicine ,Immunology and Allergy ,Cytotoxic T cell ,Animals ,Coronavirus Nucleocapsid Proteins ,Humans ,Cells, Cultured ,SARS-CoV-2 ,Vaccination ,COVID-19 ,Virology ,Mice, Inbred C57BL ,Disease Models, Animal ,medicine.anatomical_structure ,Immunization ,Humoral immunity ,Female ,Angiotensin-Converting Enzyme 2 ,030215 immunology - Abstract
The magnitude of SARS-CoV-2–specific T cell responses correlates inversely with human disease severity, suggesting T cell involvement in primary control. Whereas many COVID-19 vaccines focus on establishing humoral immunity to viral spike protein, vaccine-elicited T cell immunity may bolster durable protection or cross-reactivity with viral variants. To better enable mechanistic and vaccination studies in mice, we identified a dominant CD8 T cell SARS-CoV-2 nucleoprotein epitope. Infection of human ACE2 transgenic mice with SARS-CoV-2 elicited robust responses to H2-Db/N219-227, and 40% of HLA-A*02+ COVID-19 PBMC samples isolated from hospitalized patients responded to this peptide in culture. In mice, i.m. prime-boost nucleoprotein vaccination with heterologous vectors favored systemic CD8 T cell responses, whereas intranasal boosting favored respiratory immunity. In contrast, a single i.v. immunization with recombinant adenovirus established robust CD8 T cell memory both systemically and in the respiratory mucosa.
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- 2020
6. Retrograde migration supplies resident memory T cells to lung-draining LN after influenza infection
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J. Michael Stolley, Jason S. Mitchell, Timothy Johnston, Kevin C. Osum, Sathi Wijeyesinghe, Ryan A. Langlois, Andrew G. Soerens, Pamela C. Rosato, David Masopust, Vineet Joag, and Lalit K. Beura
- Subjects
Male ,T cell ,viruses ,Immunology ,Receptors, Antigen, T-Cell ,Mice, Transgenic ,Biology ,CD8-Positive T-Lymphocytes ,Article ,Infectious Disease and Host Defense ,Mice ,Antigen ,Orthomyxoviridae Infections ,Cell Movement ,medicine ,Immunology and Allergy ,Animals ,Antigens, Viral ,Lung ,CD69 ,T-cell receptor ,Mucosal Immunology ,respiratory system ,Antigens, Differentiation ,respiratory tract diseases ,Granzyme B ,Lymphatic system ,medicine.anatomical_structure ,Influenza A virus ,Female ,Lymph Nodes ,Immunologic Memory ,CD8 - Abstract
Stolley et al. demonstrate that the decay of lung CD8+ T cell responses after primary influenza virus infection is contemporized by the egress of TRM-phenotype T cells from the lung to the draining mediastinal LN by retrograde migration, where they form more stable residents., Numerous observations indicate that resident memory T cells (TRM) undergo unusually rapid attrition within the lung. Here we demonstrate that contraction of lung CD8+ T cell responses after influenza infection is contemporized with egress of CD69+/CD103+ CD8+ T cells to the draining mediastinal LN via the lymphatic vessels, which we term retrograde migration. Cells within the draining LN retained canonical markers of lung TRM, including CD103 and CD69, lacked Ly6C expression (also a feature of lung TRM), maintained granzyme B expression, and did not equilibrate among immunized parabiotic mice. Investigations of bystander infection or removal of the TCR from established memory cells revealed that the induction of the TRM phenotype was dependent on antigen recognition; however, maintenance was independent. Thus, local lung infection induces CD8+ T cells with a TRM phenotype that nevertheless undergo retrograde migration, yet remain durably committed to the residency program within the draining LN, where they provide longer-lived regional memory while chronicling previous upstream antigen experiences., Graphical Abstract
- Published
- 2019
7. Extrinsic MAVS signaling is critical for Treg maintenance of Foxp3 expression following acute flavivirus infection
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Jessica B. Graham, Jessica L. Swarts, Jennifer M. Lund, Michael Gale, Andrew G. Soerens, Andreia Da Costa, and Esteban Garza
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0301 basic medicine ,animal diseases ,viruses ,Down-Regulation ,Gene Expression ,chemical and pharmacologic phenomena ,Biology ,Lymphocyte Activation ,T-Lymphocytes, Regulatory ,Article ,Flavivirus Infections ,Immunophenotyping ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Immune system ,Downregulation and upregulation ,Immunity ,T-Lymphocyte Subsets ,Gene expression ,Animals ,Adaptor Proteins, Signal Transducing ,Mice, Knockout ,Multidisciplinary ,Flavivirus ,Signal transducing adaptor protein ,virus diseases ,Forkhead Transcription Factors ,biology.organism_classification ,3. Good health ,Disease Models, Animal ,030104 developmental biology ,Immunology ,Acute Disease ,Cytokines ,Th17 Cells ,Signal transduction ,West Nile virus ,West Nile Fever ,030215 immunology ,Signal Transduction - Abstract
Given the rapid spread of flaviviruses such as West Nile virus (WNV) and Zika virus, it is critical that we develop a complete understanding of the key mediators of an effective anti-viral response. We previously demonstrated that WNV infection of mice deficient in mitochondrial antiviral-signaling protein (MAVS), the signaling adaptor for RNA helicases such as RIG-I, resulted in increased death and dysregulated immunity, which correlated with a failure of Treg expansion following infection. Thus, we sought to determine if intrinsic MAVS signaling is required for participation of Tregs in anti-WNV immunity. Despite evidence of increased Treg cell division, Foxp3 expression was not stably maintained after WNV infection in MAVS-deficient mice. However, intrinsic MAVS signaling was dispensable for Treg proliferation and suppressive capacity. Further, we observed generation of an effective anti-WNV immune response when Tregs lacked MAVS, thereby demonstrating that Treg detection of the presence of WNV through the MAVS signaling pathway is not required for generation of effective immunity. Together, these data suggest that while MAVS signaling has a considerable impact on Treg identity, this effect is not mediated by intrinsic MAVS signaling but rather is likely an effect of the overproduction of pro-inflammatory cytokines generated in MAVS-deficient mice after WNV infection.
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- 2017
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8. The microwell control of embryoid body size in order to regulate cardiac differentiation of human embryonic stem cells
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Jeffrey C. Mohr, Timothy J. Kamp, Andrew G. Soerens, Gary E. Lyons, Juan J. de Pablo, James A. Thomson, Sean P. Palecek, Jianhua Zhang, and Samira M. Azarin
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Myosin Light Chains ,Time Factors ,Myosin light-chain kinase ,Organogenesis ,Cellular differentiation ,Cardiac differentiation ,Biophysics ,Cell Count ,Bioengineering ,Embryoid body ,Biology ,Article ,Cell Line ,Flow cytometry ,Biomaterials ,Immunolabeling ,medicine ,Humans ,Myocytes, Cardiac ,Embryonic Stem Cells ,Cell Size ,medicine.diagnostic_test ,Gene Expression Regulation, Developmental ,Cell Differentiation ,Embryo, Mammalian ,Flow Cytometry ,Molecular biology ,Embryonic stem cell ,Cell biology ,Mechanics of Materials ,Cell culture ,Ceramics and Composites - Abstract
The differentiation of human embryonic stem cells (hESCs) into cardiomyocytes (CMs) using embryoid bodies (EBs) is relatively inefficient and highly variable. Formation of EBs using standard enzymatic disaggregation techniques results in a wide range of sizes and geometries of EBs. Use of a 3-D cuboidal microwell system to culture hESCs in colonies of defined dimensions, 100-500 microm in lateral dimensions and 120 microm in depth, enabled formation of more uniform-sized EBs. The 300 microm microwells produced highest percentage of contracting EBs, but flow cytometry for myosin light chain 2A (MLC2a) expressing cells revealed a similar percentage (approximately 3%) of cardiomyocytes formed in EBs from 100 microm to 300 microm microwells. These data, and immunolabeling with anti-MF20 and MLC2a, suggest that the smaller EBs are less likely to form contracting EBs, but those contracting EBs are relatively enriched in cardiomyocytes compared to larger EB sizes where CMs make up a proportionately smaller fraction of the total cells. We conclude that microwell-engineered EB size regulates cardiogenesis and can be used for more efficient and reproducible formation of hESC-CMs needed for research and therapeutic applications.
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- 2010
9. Extracellular matrix promotes highly efficient cardiac differentiation of human pluripotent stem cells: the matrix sandwich method
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Gary E. Lyons, Junying Yu, Xiaojun Lian, Kunil K. Raval, Andrew G. Soerens, Amanda M. Herman, Luqia Hou, Jianhua Zhang, James A. Thomson, Timothy J. Kamp, Matthew R Barron, José Jalife, Todd J. Herron, Gisela F. Wilson, Sean P. Palecek, and Matthew Klos
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Pluripotent Stem Cells ,Epithelial-Mesenchymal Transition ,Physiology ,Cellular differentiation ,medicine.medical_treatment ,Basic fibroblast growth factor ,Cell Culture Techniques ,Bone Morphogenetic Protein 4 ,Biology ,Article ,Cell Line ,Extracellular matrix ,chemistry.chemical_compound ,medicine ,Humans ,Myocytes, Cardiac ,Induced pluripotent stem cell ,Cells, Cultured ,Matrigel ,Growth factor ,Cell Differentiation ,Embryonic stem cell ,Cell biology ,Activins ,Extracellular Matrix ,Drug Combinations ,Bone morphogenetic protein 4 ,chemistry ,Immunology ,Intercellular Signaling Peptides and Proteins ,Fibroblast Growth Factor 2 ,Proteoglycans ,Collagen ,Laminin ,Cardiology and Cardiovascular Medicine ,Signal Transduction - Abstract
Rationale: Cardiomyocytes (CMs) differentiated from human pluripotent stem cells (PSCs) are increasingly being used for cardiovascular research, including disease modeling, and hold promise for clinical applications. Current cardiac differentiation protocols exhibit variable success across different PSC lines and are primarily based on the application of growth factors. However, extracellular matrix is also fundamentally involved in cardiac development from the earliest morphogenetic events, such as gastrulation. Objective: We sought to develop a more effective protocol for cardiac differentiation of human PSCs by using extracellular matrix in combination with growth factors known to promote cardiogenesis. Methods and Results: PSCs were cultured as monolayers on Matrigel, an extracellular matrix preparation, and subsequently overlayed with Matrigel. The matrix sandwich promoted an epithelial-to-mesenchymal transition as in gastrulation with the generation of N-cadherin-positive mesenchymal cells. Combining the matrix sandwich with sequential application of growth factors (Activin A, bone morphogenetic protein 4, and basic fibroblast growth factor) generated CMs with high purity (up to 98%) and yield (up to 11 CMs/input PSC) from multiple PSC lines. The resulting CMs progressively matured over 30 days in culture based on myofilament expression pattern and mitotic activity. Action potentials typical of embryonic nodal, atrial, and ventricular CMs were observed, and monolayers of electrically coupled CMs modeled cardiac tissue and basic arrhythmia mechanisms. Conclusions: Dynamic extracellular matrix application promoted epithelial–mesenchymal transition of human PSCs and complemented growth factor signaling to enable robust cardiac differentiation.
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- 2012
10. Functional Cardiomyocytes Derived from Human Induced Pluripotent Stem Cells
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Sean P. Palecek, Andrew G. Soerens, Chad H. Koonce, Gisela F. Wilson, Timothy J. Kamp, James A. Thomson, Junying Yu, and Jianhua Zhang
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Homeobox protein NANOG ,Pluripotent Stem Cells ,Sarcomeres ,Time Factors ,Physiology ,Cellular differentiation ,Action Potentials ,Embryoid body ,Biology ,Article ,Cell Line ,SOX2 ,Transduction, Genetic ,Myocyte ,Humans ,Myocytes, Cardiac ,Induced pluripotent stem cell ,Embryonic Stem Cells ,Cell Proliferation ,Homeodomain Proteins ,SOXB1 Transcription Factors ,Isoproterenol ,Nanog Homeobox Protein ,RNA-Binding Proteins ,Cell Differentiation ,Adrenergic beta-Agonists ,Molecular biology ,Embryonic stem cell ,Myocardial Contraction ,Cell biology ,Phenotype ,Gene Expression Regulation ,Cardiology and Cardiovascular Medicine ,Octamer Transcription Factor-3 - Abstract
Human induced pluripotent stem (iPS) cells hold great promise for cardiovascular research and therapeutic applications, but the ability of human iPS cells to differentiate into functional cardiomyocytes has not yet been demonstrated. The aim of this study was to characterize the cardiac differentiation potential of human iPS cells generated using OCT4 , SOX2 , NANOG , and LIN28 transgenes compared to human embryonic stem (ES) cells. The iPS and ES cells were differentiated using the embryoid body (EB) method. The time course of developing contracting EBs was comparable for the iPS and ES cell lines, although the absolute percentages of contracting EBs differed. RT-PCR analyses of iPS and ES cell–derived cardiomyocytes demonstrated similar cardiac gene expression patterns. The pluripotency genes OCT4 and NANOG were downregulated with cardiac differentiation, but the downregulation was blunted in the iPS cell lines because of residual transgene expression. Proliferation of iPS and ES cell–derived cardiomyocytes based on 5-bromodeoxyuridine labeling was similar, and immunocytochemistry of isolated cardiomyocytes revealed indistinguishable sarcomeric organizations. Electrophysiology studies indicated that iPS cells have a capacity like ES cells for differentiation into nodal-, atrial-, and ventricular-like phenotypes based on action potential characteristics. Both iPS and ES cell–derived cardiomyocytes exhibited responsiveness to β-adrenergic stimulation manifest by an increase in spontaneous rate and a decrease in action potential duration. We conclude that human iPS cells can differentiate into functional cardiomyocytes, and thus iPS cells are a viable option as an autologous cell source for cardiac repair and a powerful tool for cardiovascular research.
- Published
- 2009
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