A5000773708- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Immune Response and Inflammation
- CAR-T cell therapy research
- Cell Adhesion Molecules Research
- Chronic Lymphocytic Leukemia Research
- Galectins and Cancer Biology
- Viral-associated cancers and disorders
- Monoclonal and Polyclonal Antibodies Research
- Glycosylation and Glycoproteins Research
- Lymphoma Diagnosis and Treatment
- Cytokine Signaling Pathways and Interactions
- Signaling Pathways in Disease
- Immunodeficiency and Autoimmune Disorders
- Hematopoietic Stem Cell Transplantation
- Platelet Disorders and Treatments
- Chromium effects and bioremediation
- Cytomegalovirus and herpesvirus research
- Invertebrate Immune Response Mechanisms
- Immune cells in cancer
- Acute Lymphoblastic Leukemia research
- Antiplatelet Therapy and Cardiovascular Diseases
- Protein Tyrosine Phosphatases
- Protein Kinase Regulation and GTPase Signaling
George Washington University
2004-2023
District of Columbia Department of Health
2023
Children's National
2005-2022
Washington University in St. Louis
2013
Washington University Medical Center
2004-2010
Hospital for Tropical Diseases
2008
Yale University
1994-2002
Howard Hughes Medical Institute
1995-2001
St. Jude Children's Research Hospital
2001
University of Tennessee Health Science Center
2001
Abstract Galectin-1 induces death of immature thymocytes and activated T cells. binds to cell-surface glycoproteins CD45, CD43, CD7, although the precise roles each receptor in cell are unknown. We have determined that CD45 can positively negatively regulate galectin-1-induced death, depending on glycosylation status CD45+ BW5147 cells lacking core 2 β-1,6-N-acetylglucosaminyltransferase (C2GnT) were resistant galectin-1 death. The inhibitory effect C2GnT− appeared require cytoplasmic...
Abstract The potency of TCR signaling can regulate the differentiation naive CD4+ T cells into Th1 and Th2 subsets. In this work we demonstrate that by low-affinity, but not high-affinity, peptide ligands selectively induces IL-4 transcription within 48 h priming cells. This early is STAT6 independent occurs before an increase in GATA-3. Furthermore, strength signal differentially affects balance NFATp NFATc DNA binding activity, thereby regulating transcription. Low-potency signals result...
Abstract Extracellular cyclophilins have been well described as chemotactic factors for various leukocyte subsets. This capacity is dependent upon interaction of with the cell surface signaling receptor CD147. Elevated levels extracellular documented in several inflammatory diseases. We propose that cyclophilins, via CD147, may contribute to recruitment leukocytes from periphery into tissues during responses. In this study, we examined whether cyclophilin-CD147 interactions might influence...
The role of STAT (signal transducer and activator transcription) proteins in T cell receptor (TCR) signaling was analyzed. STAT5 became immediately transiently phosphorylated on tyrosine 694 response to TCR stimulation. Expression the protein kinase Lck, a key complex, activated DNA binding transfected STAT5A STAT5B specific inducible elements. Lck activation confirmed Lck-deficient line which by stimulation abolished. induced interaction with subunits TCR, indicating that may be directly...
Rac2 is a hematopoietic-specific GTPase acting as molecular switch to mediate both transcriptional activation and cell morphological changes. We have examined the effect of deficiency during T activation. In Rac2(-/-) cells, proliferation was reduced upon stimulation with either plate-bound anti-CD3 or receptor-specific antigen. This defect accompanied decreased mitogen activated protein kinase extracellular signal-regulated (ERK)1/2 p38, Ca(2)+ mobilization. TCR stimulation-induced actin...
The CD45 tyrosine phosphatase plays an important role in regulating T lymphocyte activation, but the function of different isoforms is not known. cell transfectants have been prepared that express individual cells with a well-defined receptor (TCR) from D10 helper 2 clone. We find bearing low molecular weight are far more efficient responding to stimulation peptide and antigen-presenting compared high isoforms. One hypothesis for preferential activation they interact other surface antigens...
Vascular endothelial cells (ECs) can undergo dramatic phenotypic and functional alterations in response to humoral cellular stimuli. These changes promote participation the inflammatory through active recruitment of immune effector cells, increased vascular permeability, alteration tone. In an attempt define early events lymphocyte-mediated EC signaling, we investigated cytosolic-free calcium (Ca2+) single, Fluo-3-labeled human umbilical vein ECs (HUVECs), using ACAS interactive laser...
Novel therapies are urgently needed for ovarian cancer (OC), the fifth deadliest in women. Preclinical work has shown that DNA methyltransferase inhibitors (DNMTis) can reverse immunosuppressive tumor microenvironment OC. Inhibiting methyltransferases activate transcription of double-stranded (ds)RNA, including transposable elements. These dsRNAs sensors cytoplasm and trigger type I interferon (IFN) signaling, recruiting host immune cells to kill cells. Adenosine deaminase 1 (ADAR1) is...
We have recently shown that altered peptide ligands influence differentiation of CD4+ T cells into Th1 and Th2 subsets. In the present study, we examined biochemical signals in naive after priming with ligand (APL) correlate differences cytokine expression. Although observed zeta-chain phosphorylation APL-stimulated cells, other signaling events such as ZAP70 Lnk are not initiated. This pattern early correlates a distinct Ca2+ mobilization characterizes cells. By changing calcium environment...
To define the role of CD4 in modulating T cell signaling pathways and regulating Th1 Th2 differentiation, we have examined activation differentiation characteristics naive cells from mutant mice. Using peptides with differing affinities for moth cytochrome c-specific TCR, test hypothesis that differences coreceptor recruitment explain qualitatively distinct seen following high affinity agonist low altered peptide ligand (APL) ligation. We find absence during stimulation a strong does not...
Parasitic helminths induce chronic infections in their hosts although, with most human helminthiases, protective immunity gradually develops age or exposure of the host. One exception is infection hookworm, Necator americanus, where virtually no protection ensues over time. Such observations suggest these parasites have developed unique mechanisms to evade host immunity, leading us investigate role excretory/secretory (ES) products adult N. americanus manipulating immune responses....
CD45 is the predominant transmembrane tyrosine phosphatase in lymphocytes and required for efficient induction of T cell receptor signaling activation. However, regulation activity substrate specificity are poorly understood. In present study, we demonstrate a basal biochemical association with complex that regulated part by isoform expression. Further, maintenance CD45/TCR differentially following TCR ligation peptide: partial agonist peptide induces dissociation while an promotes sustained...
Abstract Gangliosides, sialic acid-containing glycosphingolipids present in the outer leaflet of plasma membranes, are produced at high levels by some tumors, actively shed into tumor microenvironment, and can be detected concentrations serum cancer patients. These tumor-shed molecules known to immunosuppressive, although mechanisms remain fully elucidated. In this study, we show that membrane enrichment human monocytes with purified exogenous gangliosides potently inhibits ligand-induced...
Background: Rapidly improving protocols for the derivation of autologous cells from stem cell sources is a welcome development. However, there are many circumstances when off-the-shelf universally immunocompatible may be needed. Embryonic (ESCs) provide unique opportunity to modify original source differentiated minimize their rejection by nonautologous hosts. Hypothesis: Immune human embryonic (hESC) derivatives can reduced downregulating leukocyte antigen (HLA) class I molecules, without...
Selectins are Ca(2+)-dependent glycoprotein receptors that mediate the adhesion of activated platelets or endothelial cells to unstimulated leukocytes. Using purified cell fractions, we examined neutrophil P-selectin-expressing and found phorbol 12-myristate 13-acetate (PMA), platelet activating factor C16 (PAF), n-formyl-met-leu-phe (fMLP) pretreatment neutrophils inhibited adhesion. Furthermore, PMA PAF were capable dissociating established resting neutrophil-activated conjugates. Since...
Journal Article B-Cell Precursor Bone Marrow Reconstitution After Transplantation Get access David Leitenberg, MD, PhD, PhD From Yale University School of Medicine, Departments Laboratory Medicine and Internal Medicine. Search for other works by this author on: Oxford Academic Google Scholar Joel M. Rappeport, MD Brian R. Smith, American Clinical Pathology, Volume 102, Issue 2, 1 August 1994, Pages 231–236, https://doi.org/10.1093/ajcp/102.2.231 Published: 01 1994 history Received: 23 July...
Tumour pathogenesis is characterized by an immunosuppressive microenvironment that limits the development of effective tumour-specific immune responses. This in part result tumour-dependent recruitment and activation regulatory cells, such as myeloid-derived suppressor cells T tumour draining lymph nodes. Shedding gangliosides has immunomodulatory properties, suggesting may be a critical factor initiating microenvironment. To better define properties on antigen-specific T-cell we have...
Abstract The TCR complex signals through a set of 10 intracytoplasmic motifs, termed immunoreceptor tyrosine-based activation motifs (ITAMs), contained within the γ-, δ-, ε-, and ζ-chains. need for this number ITAMs is uncertain. Limited contradictory studies have examined ability subsets TCR’s to signal into postthymic primary T lymphocytes. To study signaling by restricted ITAMs, we expressed in transgenic mice chimeric construct containing IAs class II MHC extracellular transmembrane...
Activation of T lymphocytes through their TCR is regulated by a delicate balance phosphorylation and dephosphorylation protein substrates tyrosine kinases (PTKs) phosphotyrosyl phosphatases, respectively. One the earliest steps in activation pathway thought to involve Src family PTKs, p56(lck) (Lck) p59(fyn) (Fyn); however, precise contribution each PTK TCR-mediated signaling remains incompletely understood. To study role Lck mature cells, antisense RNA was used inhibit its expression...