A5033194009- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Cytomegalovirus and herpesvirus research
- Renal Transplantation Outcomes and Treatments
- CAR-T cell therapy research
- SARS-CoV-2 and COVID-19 Research
- Cell Adhesion Molecules Research
- Organ Transplantation Techniques and Outcomes
- COVID-19 Clinical Research Studies
- Single-cell and spatial transcriptomics
- Inflammation biomarkers and pathways
- Monoclonal and Polyclonal Antibodies Research
- Signaling Pathways in Disease
- Cancer Immunotherapy and Biomarkers
- COVID-19 Impact on Reproduction
- Reproductive System and Pregnancy
- Transplantation: Methods and Outcomes
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Nuclear Receptors and Signaling
- Diabetes and associated disorders
- Chronic Myeloid Leukemia Treatments
- CRISPR and Genetic Engineering
- Chronic Lymphocytic Leukemia Research
- Hepatitis B Virus Studies
VA Palo Alto Health Care System
2015-2024
Stanford University
2015-2024
Palo Alto University
2017-2024
Geriatric Research Education and Clinical Center
2021-2023
Stratford University
2016-2022
Veterans Health Administration
2021
John Wiley & Sons (United States)
2020
Hanover College
2020
Hudson Institute
2020
Moss Landing Marine Laboratories
2020
The ability of antigen receptors to engage self-ligands with varying affinity is crucial for lymphocyte development. To further explore this concept, we generated transgenic mice expressing GFP from the immediate early gene Nr4a1 (Nur77) locus. was up-regulated in lymphocytes by receptor stimulation but not inflammatory stimuli. In T cells, induced during positive selection, required major histocompatibility complex maintenance, and directly correlated strength cell (TCR) stimulus. Thus, our...
Tregs expressing the transcription factor FOXP3 are critical for immune homeostasis. The costimulatory molecule CD28 is required optimal activation and function of naive T cells; however, its role in Treg has been difficult to dissect, as thymic development, blockade CD28-ligand interactions confounding effects trans on nonregulatory cells. To address this question, we created Treg-specific Cd28 conditional knockout mice. Despite presence normal numbers FOXP3+ cells, these animals...
We report here a mAb, 14-2, reactive with TCRs that include V beta 14. The frequency of 14+ T cells varies CD4 and CD8 subset is controlled by the H-2 genes. Thus CD8+ from H-2b mice approximately 2.3% while expressing K kappa greater than 8% cells. In all strains examined, 7-8% CD4+ express frequent usage 14 in kappa-expressing result preferential positive selection as demonstrated analysis radiation chimeras. These studies demonstrate H-2-dependent occurs unmanipulated mice. Furthermore,...
Intercellular adhesion molecule (ICAM) 1/CD54 plays an important role in T cell dependent B activation and for function of lymphocytes as antigen-presenting cells. ICAM-1 expression is upregulated a consequence lymphocyte antigen receptor (BCR) signaling, thereby serving to render antigen-stimulated cells more receptive cell-mediated costimulatory signals. We have investigated BCR-induced the Icam-1 gene primary lines found it be on transcription factor EGR1. transcription, induced by BCR...
Mutations in the tumor-suppressor gene phosphatase and tensin homolog deleted on chromosome 10 (Pten) are associated with multiple cancers humans, including T cell malignancies. Targeted deletion of Pten cells induces both a disseminated "mature phenotype" lymphoma lymphoproliferative autoimmune syndrome mice. Here, we have shown that these two diseases separable mediated by lineage distinct developmental stages. Loss PTEN was found to be powerful driver lymphomagenesis within thymus...
Abstract Research on human immune responses frequently involves the use of peripheral blood mononuclear cells (PBMC) immediately, or at significantly delayed timepoints, after collection. This requires PBMC isolation from whole and cryopreservation for some applications. It is important to standardize protocols collection, isolation, cryopreservation, thawing that maximize survival functionality time analysis. resource includes detailed describing collection tubes, using a density gradient,...
Regulatory T cells (Tregs) are a subset of CD4(+) that maintain immune tolerance in part by their ability to inhibit the proliferation conventional (Tconvs). The role TCR and downstream signaling pathways required for this suppressive function Tregs not fully understood. To yield insight into how TCR-mediated signals influence Treg function, we assessed with altered capacity Tconv proliferation. Mature deficient Src homology 2 domain containing leukocyte protein 76 kDa (SLP-76), an adaptor...
Transplant recipients who develop COVID-19 may be at increased risk for morbidity and mortality. Determining the status of antibodies against SARS-CoV-2 in both candidates will important to understand epidemiology clinical course this population. While there are multiple tests detect SARS-CoV-2, their performance is variable. Tests vary according platforms antigenic targets which make interpretation results challenging. Furthermore, some assays, sensitivity specificity less than optimal....
Solid organ transplantation is a life-saving treatment for people with end-stage disease. Immune-mediated transplant rejection common complication that decreases allograft survival. Although immunosuppression required to prevent rejection, it also increases the risk of infection. Some infections, such as cytomegalovirus and BK virus, can promote inflammatory gene expression further tip balance toward rejection. virus other infections induce damage resembles clinical pathology this...
The immediate-early gene egr-1 encodes a transcription factor (EGR1) that links B-cell antigen receptor (BCR) signals to downstream activation events through the regulation of previously unidentified target genes. Here we identify encoding lymphocyte homing and migration protein CD44 as EGR1 in B cells. BCR-induced increases mRNA expression levels are shown occur EGR1-expressing but not nonexpressing subclones line WEHI-231. Kinetics appearance nuclear precede induction within 30 min after...
The adapter protein SH2 domain-containing leukocyte of 76 kDa (SLP-76) is an essential mediator signaling from the T-cell antigen receptor (TCR). We report here that SLP-76 also mediates downstream integrins in T cells and SLP-76-deficient fail to support adhesion integrin ligands. In response both TCR stimulation, relocalizes surface microclusters colocalize with phosphorylated proteins. Disruption recruitment named LAT (linker for activation cells) inhibits clustering but not integrins....
The presence and structure of nicotinic acetylcholine receptor (nAChR) in the thymus has been a subject interest for many years because its possible role pathogenesis autoimmune disease myasthenia gravis. Using polymerase chain reaction with primers specific alpha-chain nAChR (nAChR-alpha), an 880-bp homologous band was found after amplification cDNA prepared from mouse thymus, thymic medullary cortical epithelial cell lines, but not thymocytes or kidney. Sequencing product lines showed...
The SH2 domain containing leukocyte phosphoprotein of 76 kD (SLP-76) is critical for pre-TCR–mediated maturation to the CD4+CD8+ double positive (DP) stage in thymus. absolute block SLP-76null mice at CD4−CD8−CD44−CD25+ (double-negative 3, DN3) has hindered our understanding role this adaptor αβ TCR-mediated signal transduction primary thymocytes and peripheral T lymphocytes. To evaluate requirements SLP-76 these events, we used a cre-loxP approach generate that conditionally delete after...
Transcription factors regulate T cell fates at every stage of development and differentiation. Members the Foxp family forkhead transcription are essential for normal lineage development; Foxp3 is required regulatory generation function, Foxp1 necessary maintenance naïve cells. Foxp4, an additional member family, highly homologous to has been shown dimerize with other proteins. We report initial characterization Foxp4 in lymphocytes. expressed both thymocytes peripheral CD4(+) CD8(+) used a...
Abstract To ensure immune tolerance, regulatory T cell (Treg) numbers must be maintained by division. This process has been thought to strictly dependent on the Treg TCR interacting with MHC class II. In this study, we report that division does not absolutely require cell-autonomous signaling in vivo, depending degree of IL-2–mediated stimulation provided. At steady state IL-2 levels, Tregs divide. However, when given exogenous or STAT5 is selectively activated Tregs, can occur independently...
Cytomegalovirus (CMV) is a major cause of morbidity and mortality in solid organ transplant recipients. Approximately 60% adults are CMV seropositive, indicating previous exposure. Following resolution the primary infection, remains latent state. Reactivation controlled by memory T cells healthy individuals; recipients have reduced cell function due to chronic immunosuppressive therapies. In this study, CD8+ responses polypeptides immediate-early-1 pp65 were analyzed 16 CMV-seropositive...