A5061605555- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Melanoma and MAPK Pathways
- Cutaneous Melanoma Detection and Management
- Research on Leishmaniasis Studies
- Cell Adhesion Molecules Research
- Immune Response and Inflammation
- Immune cells in cancer
- Phagocytosis and Immune Regulation
- CAR-T cell therapy research
- Trypanosoma species research and implications
- Cancer Immunotherapy and Biomarkers
- RNA Interference and Gene Delivery
- Dermatology and Skin Diseases
- Protein Degradation and Inhibitors
- Advanced biosensing and bioanalysis techniques
- Advanced Fluorescence Microscopy Techniques
- Nanoplatforms for cancer theranostics
- Cellular Mechanics and Interactions
- Monoclonal and Polyclonal Antibodies Research
- Diabetes and associated disorders
- Chemokine receptors and signaling
- Apelin-related biomedical research
- IL-33, ST2, and ILC Pathways
Cornell University
2021-2025
Ithaca College
2023
University of Rochester Medical Center
2008-2022
New York State College of Veterinary Medicine
2021
University of Rochester
2010-2020
Institute of Biomedical Science
2008
MRC Human Immunology Unit
2007
University of Oxford
1994-2007
University of California, San Francisco
1995-2000
Cytel (United States)
1999
Purified rat CD4+ T cells were activated in vitro the presence or absence of glucocorticoid dexamethasone. They then expanded IL-2 and subsequently restimulated, this time hormone. The results indicate that exposure to dexamethasone primary stimulation changed cytokine synthesis induced by secondary stimulation. mRNA levels for IL-4, IL-10, IL-13 all increased pretreatment, whereas IFN-gamma TNF-alpha was diminished. Further studies which IL-4 used together with showed potentiated effect...
CD73 (5'-ectonucleotidase) is expressed by two distinct mouse CD4 T cell populations: CD25+ (FoxP3+) regulatory (Treg) cells that suppress proliferation but do not secrete IL-2, and CD25- uncommitted primed precursor Th (Thpp) IL-2 in standard Treg suppressor assays. on both Thpp converted extracellular 5'-AMP to adenosine. Adenosine suppressed cytokine secretion of Th1 Th2 effector cells, even when target were activated anti-CD3 anti-CD28. This represents an additional suppressive mechanism...
Interleukin (IL)-10 is a pleiotropic cytokine which inhibits broad array of immune parameters including T helper cell type 1 (Th1) production, antigen presentation, and antigenspecific proliferation. To understand the consequences altered expression IL-10 in models autoimmune disease, response to infectious agents, tumors, we developed transgenic mice expressing under control IL-2 promoter. Upon vitro stimulation, spleen cells from unimmunized secrete higher levels lower amounts IFN-γ than...
A number of investigations have established the critical role interleukin 4 (IL-4) in mediating development T helper (Th)2 effector cells vitro and vivo. Despite intensive study, origin IL-4 required for Th2 priming differentiation remains unclear. Natural killer (NK)1.1+ alpha/beta cell receptor+ T(NT) cells, a unique lineage capable producing large amounts after activation vivo, are important candidates directing priming. These selected by nonpolymorphic major histocompatibility complex...
The efficient trafficking of immune cells into peripheral nonlymphoid tissues is key to enact their protective functions. Despite considerable advances in our understanding cell migration secondary lymphoid organs, real-time leukocyte recruitment inflamed not well characterized. conventional multistep paradigm extravasation depends on CD18 integrin–mediated events such as rapid arrest and crawling the surface endothelium transmigration through endothelial layer. Using enhanced...
CD134 (OX40) is a member of the TNF receptor family that expressed on activated T lymphocytes. cells from mice lack expression made strong responses to range challenges, but they showed impaired proliferation in response direct stimulation through TCR with monoclonal anti-CD3epsilon Ab. CD134-deficient controlled infection Leishmania major, Nippostrongylus brasiliensis, and Theiler's murine encephalomyelitis virus, overtly normal Ab variety antigens. Thus, not essential for many cell vivo,...
Abstract Protective immunity against Leishmania major generated by DNA encoding the LACK (Leishmania homologue of receptor for activated C kinase) Ag has been shown to be more durable than vaccination with protein plus IL-12. One mechanism account this may selective ability induce CD8+ IFN-γ-producing T cells. In regard, we previously reported that depletion cells in DNA-vaccinated mice abrogated protection when infectious challenge was done 2 wk postvaccination. study, extend these findings...
CTLA-4 is constitutively expressed by CD4(+)CD25(+)Foxp3(+) Treg but its precise role in function not clear. Although blockade of interferes with function, studies using CTLA-4-deficient have failed to reveal an essential requirement for suppression vivo. Conditional deletion Foxp3(+) T cells disrupts immune homeostasis vivo the processes disrupted been determined. We demonstrate that expression control lymphopenia-induced CD4 T-cell expansion. Despite IL-10 expression, were unable expansion...
Th cells are the major effector in transplant rejection and can be divided into Th1, Th2, Th17, Treg subsets. differentiation is controlled by transcription factor expression, which driven positive negative cytokine chemokine stimuli at time of T cell activation. Here we discovered that platelet 4 (PF4) a regulator Th17 differentiation. PF4-deficient platelet-deficient mice had exaggerated immune responses to cardiac transplantation, including increased numbers infiltrating plasma IL-17....
CD4 + CD25 Forkhead box P3 (Foxp3) regulatory T cells (Tregs) control immune responses to self and foreign antigens in secondary lymphoid organs at tissue sites of inflammation. Tregs can modify the function many have been proposed block early proliferation, differentiation, effector function. Acute ablation has revealed rapid cytokine production immediately after Treg removal, suggesting that may regulate acutely rather than regulating programming for We developed vitro vivo models enabled...
Interleukin 4 (IL-4) plays a central role in the orchestration of Type 2 immunity. During T cell activation lymph node, IL-4 promotes Th2 differentiation and inhibits Th1 generation. In inflamed tissue, signals promote innate adaptive Type-2 immune recruitment effector function, positively amplifying local response. this study, we identify an additional negative regulatory for limiting cells to tissues. To test effects on inflammation subsequent differentiation, transiently blocked during...
Immune cells are highly dynamic and able to migrate through environments with diverse biochemical mechanical compositions. Their migration has classically been defined as amoeboid under the assumption that it is integrin independent. Here, we show activated primary Th1 T require both confinement extracellular matrix proteins efficiently. This mediated small focal adhesions composed of same associated canonical mesenchymal cell adhesions, such integrins, talin, vinculin. These furthermore,...
Leishmaniasis is a parasitic disease that widely prevalent in many tropical and sub-tropical regions of the world. Infection with Leishmania has been recognized to induce striking acceleration Human Immunodeficiency Virus Type 1 (HIV-1) infection coinfected individuals through as yet incompletely understood mechanisms. Cells monocyte/macrophage lineage are predominant cell types by both pathogens. Monocytes macrophages contain extremely low levels deoxynucleoside triphosphates (dNTPs) due...
The extracellular matrix (ECM) is extensively remodeled during inflammation providing essential guidance cues for immune cell migration and signals activation survival. There increasing interest in the therapeutic targeting of ECM to mitigate chronic inflammatory diseases enhance access tumor microenvironment. T cells utilize as a scaffold interstitial migration, dependent on expression matrix-binding integrins V1/V3 tissue display respective RGD-containing ligands. specific components...
ABSTRACT The spatial organization of adaptive immune cells within lymph nodes is critical for understanding responses during infection and disease. Here, we introduce AIR-SPACE, an integrative approach that combines high-resolution transcriptomics with paired, high-fidelity long-read sequencing T B cell receptors. This method enables the simultaneous analysis cellular transcriptomes receptor (AIR) repertoires their native context. We applied AIR-SPACE to mouse popliteal at five distinct time...
Interferon γ (IFN-γ) has been implicated in T helper type 1 (Th1) cell development through its ability to optimize interleukin 12 (IL-12) production from macrophages and IL-12 receptor expression on activated cells. Various systems have suggested a role for IFN-γ derived the innate immune system, particularly natural killer (NK) cells, mediating Th1 differentiation vivo. We tested this requirement by reconstituting doubly deficient mice with wild-type CD4+ cells challenging pathogens that...
Loss of the kinase Itk in activated T cells disrupts actin accumulation at immunological synapse, compromising cell activation.