A5086723362- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Immune Response and Inflammation
- CAR-T cell therapy research
- Electrocatalysts for Energy Conversion
- Immunodeficiency and Autoimmune Disorders
- Blood groups and transfusion
- IL-33, ST2, and ILC Pathways
- Microbial infections and disease research
Children's Hospital of Philadelphia
2024
University of Pennsylvania
2024
Hospital of the University of Pennsylvania
2023
University of Colorado Denver
2013-2021
University of Colorado Anschutz Medical Campus
2016-2021
University of Denver
2013
Abstract Virtual memory cells (VM) are an antigen-specific, phenotype CD8 T-cell subset found in lymphoreplete, unchallenged mice. Previous studies indicated that VM were the result of homeostatic proliferation (HP) resembling observed a lymphopenic environment. Here we demonstrate HP is ongoing lymphoreplete mice, degree which dictated by number naive T with sufficiently high affinity for self-antigen interacting peripheral IL-15. cell transcriptional profiles suggest capacity to mediate...
Various populations of memory phenotype CD8(+) T cells have been described over the last 15-20 y, all which possess elevated effector functions relative to naive cells. Using a technique for isolating Ag-specific from unprimed hosts, we recently identified new subset cells, specific nominal Ag, but phenotypically and functionally similar arising as result homeostatic proliferation. We show in this study that these virtual (VM) are independent previously innate their response IL-15 trans...
Adaptive immunity requires the expansion of high-affinity lymphocytes from a heterogeneous pool. Whereas current models explain this through signal transduction, we hypothesized that antigen affinity tunes discrete metabolic pathways to license clonal lymphocyte dynamics. Here, identify nicotinamide adenine dinucleotide (NAD) biosynthesis as biochemical hub for T cell receptor affinity-dependent metabolome. Through central anabolic role, found NAD governs quiescence exit checkpoint, thereby...
The relationship between B cells and CD4 T has been carefully studied, revealing a collaborative effort in which promote the activation, differentiation, expansion of while so-called "helper" provide signals to cells, influencing their class switching fate. Interactions CD8 are not as well although exhibit an accelerated contraction after certain infections B-cell-deficient mice. Here, we find that significantly enhance primary cell responses vaccination. Moreover, memory numbers function...
It is common practice for researchers to use antibodies remove a specific cell type infer its function. However, it difficult completely eliminate and there often limited or no information as how the cells which survive depletion are affected. This particularly important CD8+ T two reasons. First, they more resistant mAb-mediated than other lymphocytes. Second, targeting either CD8α CD8β chain could induce differential effects. We show here that commonly used mAbs, against subunit, can...
Abstract Endogenous antigen-specific CD8 T cells have been detected within B cell zones of the splenic white pulp during primary response to multiple infections. The physiologic implications recruitment are unknown. However, such localization may be beneficial for immunity in ways, including, but not limited to: 1) direct cell-mediated costimulation cells, 2) cell-derived signals lowering threshold help required from CD4 follicular helper (Tfh) maturation, and/or 3) support Tfh cells. We...
ABSTRACT Thymic selection predisposes naive T cells to particular outcomes when challenged later with cognate antigen, whether the antigen is self or foreign. This suggests that there an inherent heterogeneity of functioning among within population (both CD4 and CD8s), each cell, as part its thymic development, given a certain ‘programming’ which will affect eventual fate decisions. In this project, we looked at primary effects imprinting on conversion naïve into Tregs. Further, using...
Abstract A long-sought goal of vaccine development is to produce robust cytotoxic T cell responses prevent future infection. This can be accomplished via live-attenuated vaccines, with the caveat poor stability and pathogenic reversion concerns. However, a combined TLR agonist/CD40 agonist adjuvant mix (TLR/CD40 vaccination) pioneered by our lab produces potent protective CD8+/CD4+ memory. mechanistic underpinnings memory are unknown. Recent work suggests that metabolic state plays crucial...
Abstract Various populations of memory phenotype CD8+ T cells have been described over the last 15-20 years, all which possess elevated effector functions relative to naïve cells. Using a technique for isolating antigen specific from unprimed hosts, we recently identified new subset cells, nominal antigen, but phenotypically and functionally similar arising as result homeostatic proliferation (HP). We show here that these “Virtual Memory” are independent previously “innate memory” their...
The close relationship between B cells and CD4 T has been carefully studied, revealing a collaborative effort, where promote the activation, differentiation, expansion of cells, while so-called “helper” provide signals to influencing their class-switching fate. Interactions CD8 are not as well although do exhibit an accelerated contraction after certain infections in cell-deficient mice. Here, we found that significantly enhance primary cell responses following vaccination. Moreover, memory...