A5062264975- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Diabetes and associated disorders
- Pancreatic function and diabetes
- Cancer Immunotherapy and Biomarkers
- Hematopoietic Stem Cell Transplantation
- Monoclonal and Polyclonal Antibodies Research
- RNA Interference and Gene Delivery
- CAR-T cell therapy research
- Immune Response and Inflammation
- IL-33, ST2, and ILC Pathways
University of Minnesota Medical Center
2016-2024
University of Minnesota
2015-2024
Twin Cities Orthopedics
2017
Type 1 diabetes is caused by autoreactive T cell-mediated β cell destruction. Even though co-inhibitory receptor programmed death-1 (PD-1) restrains autoimmunity, the expression and regulation of its cognate ligands on remains unknown. Here, we interrogated cell-intrinsic death ligand-1 (PD-L1) in mouse human islets. We measured a significant increase level PD-L1 surface frequency
Numerous observations indicate that resident memory T cells (TRM) undergo unusually rapid attrition within the lung. Here we demonstrate contraction of lung CD8+ cell responses after influenza infection is contemporized with egress CD69+/CD103+ to draining mediastinal LN via lymphatic vessels, which term retrograde migration. Cells retained canonical markers TRM, including CD103 and CD69, lacked Ly6C expression (also a feature TRM), maintained granzyme B expression, did not equilibrate among...
Abstract Programmed death-1 (PD-1) promotes T cell tolerance. Despite therapeutically targeting this pathway for chronic infections and tumors, little is known about how different subsets are affected during blockade. We examined PD-1/PD ligand 1 (PD-L1) regulation of self-antigen–specific CD4 CD8 cells in autoimmune-susceptible models. PD-L1 blockade increased insulin-specific effector type diabetes. However, anergic islet-specific were resistant to Additionally, was critical induction, but...
Abstract Monoclonal antibodies specific for foreign antigens, auto-antigens, allogeneic antigens and tumour neo-antigens in the context of major histocompatibility complex II (MHCII) are highly desirable as novel immunotherapeutics. However, there is no standard protocol efficient generation monoclonal that recognize peptide MHCII, only a limited number such reagents exist. In this report, we describe an approach screening bound to MHCII. This exploits use recombinant peptide:MHC monomers...
Infusion of in vitro-derived T cell progenitor (proT) therapy with hematopoietic stem transplant aids the recovery thymus damaged by total body irradiation. To understand interaction between proTs and thymic microenvironment, WT mice were lethally irradiated given cell-deficient (Rag1-/-) marrow vitro-generated proTs, limiting mature development to infused proTs. ProTs within host led a significant increase epithelial cells (TECs) day 21 after transplant, increasing actively cycling TECs....
Organ transplants are rapidly rejected because T cells in the recipient attack foreign MHC molecules on graft. The robustness of cell response to histoincompatible tissue is not understood. We found that mice have many small populations with Ag receptors specific for a class II molecule type loaded peptides from leukocytes These proliferated modestly after skin transplantation and underwent relatively weak functional differentiation compared stimulated by vaccine. Thus, potency likely due...
Abstract The inhibitory receptor programmed death (PD)-1 and its ligand PD-L1 regulate T cell function to limit autoimmunity. PD-1 is highly expressed on exhausted cells, limiting their antiviral or antitumor activity. Even though pathway blockade has gained momentum in cancer treatment, it unclear how PD-1/PD-L1 impacts different subsets. We examined the effects of self-reactive CD4+ cells mouse models varying autoimmune susceptibilities. used insulin-peptide/MHC Class II tetramers track...
Abstract Type 1 diabetes (T1D) results from T cell-mediated destruction of insulin-producing pancreatic β cells. Individuals with long-term disease are at risk developing life-threatening complications. cell replacement is a therapy for T1D but limited by recurrent autoreactive targeted death. Thus, cells better equipped to inhibit local responses may survive longer in autoimmune recipients. Programmed-death (PD-1) signaling through its ligand PD-L1 inhibits cells, and serve as prominent...
Abstract Type 1 diabetes (T1D) results from lymphocyte-mediated destruction of insulin-producing pancreatic beta cells. Islet-reactive CD4 T cells are critical mediators disease. Here, we investigated the phenotype and regulation insulin-specific bulk in diabetes-prone (NOD) diabetes-resistant (NOR or B6.g7) mice. We utilized dual color tetramer staining with enriment techniques to enumerate NOD, NOR B6.g7 To test whether there inherent differences cell compartment between strains,...