A5046685448- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Immune Response and Inflammation
- SARS-CoV-2 and COVID-19 Research
- NF-κB Signaling Pathways
- interferon and immune responses
- Monoclonal and Polyclonal Antibodies Research
- CAR-T cell therapy research
- Influenza Virus Research Studies
- Cancer Immunotherapy and Biomarkers
- vaccines and immunoinformatics approaches
- Vaccine Coverage and Hesitancy
- COVID-19 Clinical Research Studies
- Cell Adhesion Molecules Research
- HIV Research and Treatment
- Cell death mechanisms and regulation
- Immunodeficiency and Autoimmune Disorders
- Biochemical and Structural Characterization
- Cytomegalovirus and herpesvirus research
- Herpesvirus Infections and Treatments
- Immune cells in cancer
- COVID-19 epidemiological studies
- Chemical Synthesis and Analysis
- Glycosylation and Glycoproteins Research
University of Toronto
2016-2025
Public Health Ontario
2024-2025
Centre for Social Innovation
2016-2021
Canada Research Chairs
2003-2018
Ontario Institute for Cancer Research
2011
Princess Margaret Cancer Centre
2011
University Health Network
2011
Institute of Neuroimmunology of the Slovak Academy of Sciences
2009
Muscular Dystrophy Canada
2008
University of New Brunswick
2004
Abstract A costimulatory member of the TNFR family, 4-1BB, is expressed on activated T cells. Although some reports have suggested that 4-1BB primarily involved in CD8 cell activation, this report we demonstrate both CD4 and cells respond to ligand (4-1BBL) with similar efficacy. TCR transgenic up-regulate OX40, CD27 4-1BBL-mediated costimulation during a primary response peptide Ag. 4-1BBL enhanced proliferation, cytokine production, CTL effector function To compare vs responses under...
Abstract The interaction of the T cell surface protein CD28 with its ligand, B7-1 or B7-2, provides a critical costimulatory signal for activation. cells from CD28- mice are deficient in variety responses, including those to lectins and allogeneic spleen cells. However, some immune responses do occur mice, suggesting existence alternate pathways. In this work, we show that purified respond B lymphomas expressing 4-1BB ligand (4-1BBL), member TNF gene family. This response is inhibited by...
4-1BB ligand (4-1BBL) is a member of the tumor necrosis factor (TNF) family expressed on activated antigen-presenting cells. Its receptor, 4-1BB, TNF receptor CD4 and CD8 T We have produced soluble form 4-1BBL using baculovirus expression system. When coimmobilized plastic with anti-CD3, induces interleukin (IL)-2 production by resting CD28+ or CD28− cells, indicating that can function independently other cell surface molecules, including CD28, in costimulation activation. At low...
I-Ad, purified from A20-1.11 cells by affinity chromatography, was incorporated into supported planar membranes incubation of I-Ad-containing phospholipid vesicles with clean glass coverslips. Such present a peptide digest ovalbumin to the ovalbumin-specific, I-Ad-restricted T-cell hybridoma 3DO-54.8, resulting in antigen-specific release interleukin 2. However, when same material provided form small unilamellar vesicles, no response obtained. Antigen presentation inhibited monoclonal...
Abstract 4-1BB ligand (4-1BBL) is a member of the TNF family expressed on activated APC. 4-1BBL binds to (CD137) CD4 and CD8 T cells in conjunction with strong signals through TCR provides CD28-independent costimulatory signal leading high level IL-2 production by primary resting cells. Here we report immunological characterization mice lacking both CD28. 4-1BBL−/− mount neutralizing IgM IgG responses vesicular stomatitis virus that are indistinguishable from those wild-type mice. show...
Abstract In this report, we demonstrate that CD28−/− mice are severely impaired in the initial expansion of Db/NP366-374-specific CD8 T cells response to influenza virus infection, whereas 4-1BB ligand (4-1BBL)−/− show no defect primary cell virus. contrast, 4-1BBL−/− a decrease late response. Upon secondary challenge with virus, number compared wild-type such level during vivo is reduced response, concomitant reduction CTL effector function. Ab responses, as well CD4 unaffected by 4-1BBL...
Abstract During an acute immune response, CD8 T cells undergo rapid expansion followed by a contraction phase during which the majority of activated die, leaving few survivors to persist as memory cells. The regulation cell survival is critical at each stage this response. 4-1BB, TNFR family member, has been implicated in prolonging and cells; however, precise mechanisms 4-1BB sustains are incompletely understood. Upon aggregation on cells, associates with two TNFR-associated factors (TRAF),...
BACKGROUNDLimited information is available on the impact of immunosuppressants COVID-19 vaccination in patients with immune-mediated inflammatory diseases (IMID).METHODSThis observational cohort study examined immunogenicity SARS-CoV-2 mRNA vaccines adult bowel disease, rheumatoid arthritis, ankylosing spondylitis, or psoriatic without maintenance immunosuppressive therapies. Ab and T cell responses to SARS-CoV-2, including neutralization against variants, were determined before after 1 2...
CD137 (4-1BB)-activating receptor represents a promising cancer immunotherapeutic target. Yet, the cellular program driven by and its role in immune surveillance remain unresolved. Using T cell-specific deletion agonist antibodies, we found that modulates tumor infiltration of CD8+-exhausted (Tex) cells expressing PD1, Lag-3, Tim-3 inhibitory receptors. cell-intrinsic, TCR-independent signaling stimulated proliferation terminal differentiation Tex precursor through mechanism involving RelA...
Abstract Previous studies have reported impaired humoral responses after SARS-CoV-2 mRNA vaccination in patients with immune-mediated inflammatory diseases (IMIDs), particularly those treated anti-TNF biologics. We previously that IMID diagnosed bowel disease, psoriasis, psoriatic arthritis, ankylosing spondylitis, or rheumatoid arthritis exhibited greater waning of Ab and T cell than healthy control subjects vaccine dose 2. Fewer data are available on the effects third fourth doses. This...
Abstract 4-1BB (CD137) is a costimulatory member of the TNFR family expressed on activated T cells. Its ligand, 4-1BBL, APC. In mouse, CD8 cells are preferentially by agonistic anti-murine Abs. However, murine 4-1BBL can stimulate both CD4 and To date, there only limited data effects human cell responses. further understand role in responses, we compared responses to transfected plus TCR-mediated stimulation. Both responded 4-1BBL. The presence APC led increased expansion, cytokine...
K46J B lymphomas express a T cell costimulatory activity that is not inhibited by CTLA-4Ig, anti-B7-1, anti-B7-2, anti-intercellular adhesion molecule 1 or antibodies to heat stable antigen. In this paper we report mediated at least in part 4-1BB ligand, member of the tumor necrosis factor (TNF) gene family binds 4-1BB, activation antigen with homology TNF/nerve growth receptor family. A fusion protein between and alkaline phosphatase (4-1BB-AP) blocks both an antigen-specific system...
Abstract Mice deficient in OX40 or 4-1BB costimulatory pathways show defects T cell recall responses, with predominant effects on CD4 vs CD8 cells, respectively. However, OX40L can also stimulate cells and 4-1BBL influence raising the possibility of redundancy between two TNFR family costimulators. To test this possibility, we generated mice both OX40L. In an adoptive transfer model, expressed sequentially response to immunization, little no overlap timing their expression. Under same...
Abstract Mice lacking CD137L (4-1BBL) show normal primary expansion and contraction of the CD8+ T cell response to influenza virus, but exhibit a defect in Ag-specific numbers at 3–6 wk postinfection. Previous results showed that decrease this model is not due programming during expansion. Thus, it appears 4-1BB/4-1BBL interactions control number surviving effector memory cells, late response. In report, we asked how 4-1BB on cells could play role after Ag has apparently been cleared from...