A5038423187- T-cell and B-cell Immunology
- Diabetes and associated disorders
- Immune Cell Function and Interaction
- Monoclonal and Polyclonal Antibodies Research
- Immunotherapy and Immune Responses
- Pancreatic function and diabetes
- Diabetes Management and Research
- Immunodeficiency and Autoimmune Disorders
- vaccines and immunoinformatics approaches
- Rheumatoid Arthritis Research and Therapies
- Systemic Lupus Erythematosus Research
- Cell Adhesion Molecules Research
- Immune Response and Inflammation
- Food Allergy and Anaphylaxis Research
- Proteoglycans and glycosaminoglycans research
- Toxin Mechanisms and Immunotoxins
- Cancer Immunotherapy and Biomarkers
- Diabetes Treatment and Management
- Glycosylation and Glycoproteins Research
- CAR-T cell therapy research
- Celiac Disease Research and Management
- Allergic Rhinitis and Sensitization
- Atherosclerosis and Cardiovascular Diseases
- Respiratory viral infections research
- Viral gastroenteritis research and epidemiology
Benaroya Research Institute
2016-2025
Immune Tolerance Network
2014-2025
Virginia Mason Medical Center
2011-2023
Seattle University
1993-2023
Indianapolis Zoo
2020
University of Washington
2006-2019
Translational Research Institute
2019
Ibero American University
2016
Center for Rheumatology
2012
University of Pittsburgh Medical Center
2012
Autoreactive memory T lymphocytes are implicated in the pathogenesis of autoimmune diseases. Here we demonstrate that disease-associated autoreactive cells from patients with type-1 diabetes mellitus or rheumatoid arthritis (RA) mainly CD4+ CCR7- CD45RA- effector (T(EM) cells) elevated Kv1.3 potassium channel expression. In contrast, other antigen specificities these patients, healthy individuals and disease controls, express low levels predominantly naïve central-memory (T(CM)) cells. T(EM)...
Abstract We examined the association of individual HLA genes with rheumatoid arthritis (RA), using oligonucleotide probes that identified both DR4‐associated and non–DR4‐associated genes. Two distinct HLA–DRβ alleles (Dw4 Dw14) were found in DR4+ RA patients compared controls 50% versus 17%; Dw14 35% 5%; total DR4 73% 30%), indicating these 2 are independent susceptibility Remarkably, majority DR4– also demonstrated a linear DNA sequence, apparently “shuffled” between different alleles, an...
CCR6 + myelin-reactive T cells from patients with multiple sclerosis secrete inflammatory cytokines compared to healthy subjects, showing a distinct pathogenic gene expression profile and sharing transcriptome homology encephalitogenic CD4 isolated mice experimental autoimmune encephalitis.
BACKGROUND. Type 1 diabetes (T1D) results from destruction of pancreatic β cells by autoreactive effector T cells. We hypothesized that the immunomodulatory drug alefacept would result in targeted quantitative and qualitative changes prolonged preservation endogenous insulin secretion remaining patients with newly diagnosed T1D.
Biologic treatment of T1D typically results in transient stabilization C-peptide levels (a surrogate for endogenous insulin secretion) some patients, followed by progression at the same rate as untreated control groups. Here, we used integrated systems biology and flow cytometry approaches with clinical trial blood samples to elucidate pathways associated subjects treated anti-CD3 monoclonal antibody teplizumab. We identified a population CD8 T cells that accumulated best response...
Antigen-specific T helper cells present in peripheral blood at very low frequencies are capable of rapid clonal expansion during antigenic challenge. The exquisite specificity this response provides for activation and a select cohort cells, feature we have used to directly identify quantify human epitope-specific from blood. Soluble tetramerized class II MHC molecules, loaded with an immunodominant peptide hemagglutinin (HA) labeled fluorescent dyes, were constructed antigen-specific...
Antigen-specificity is a hallmark of adaptive T cell-mediated immune responses. CD4 + CD25 FOXP3 regulatory cells (T R ) also require activation through the cell receptor for function. Although these antigen-specific activation, they are generally able to suppress bystander responses once activated. This raises possibility that may be useful therapeutically by localizing generalized suppressive activity tissues expressing select target antigens. Here, we demonstrate specific particular...
Intestinal epithelial cells express a low level of HLA class II molecules constitutively, with elevated levels seen in the setting mucosal inflammation including inflammatory bowel disease. The ability intestinal to act as antigen presenting for alphabeta CD4(+) T lymphocytes was examined through molecular analysis processing pathway. We have shown that contain abundant constitutive cathepsin proteases proven function mediated presentation. Activation these by gamma-IFN induced expression...
The autoimmune process that destroys the insulin-producing pancreatic beta cells in type 1 diabetes (T1D) is targeted at insulin and its precursor, proinsulin. T recognize proximal A-chain of human were identified recently lymph nodes subjects who had T1D. To investigate specificity proinsulin-specific T1D, we isolated CD4(+) cell clones to proinsulin from blood a donor recognized naturally processed, HLA DR4-restricted epitope within first 13 amino acids (A1-13) insulin. recognition was...
OBJECTIVE To investigate if recurrent autoimmunity explained hyperglycemia and C-peptide loss in three immunosuppressed simultaneous pancreas-kidney (SPK) transplant recipients. RESEARCH DESIGN AND METHODS We monitored autoantibodies autoreactive T-cells (using tetramers) performed biopsy. The function of was studied with vitro vivo assays. RESULTS Autoantibodies were present pretransplant persisted on follow-up one patient. They appeared years after transplantation but before the...
An association has previously been shown between antibiotic-refractory Lyme arthritis, the human histocompatibility leukocyte antigen (HLA)-DR4 molecule, and T cell recognition of an epitope Borrelia burgdorferi outer-surface protein A (OspA163-175). We studied frequencies HLA-DRB1-DQA1-DQB1 haplotypes in 121 patients with or antibiotic-responsive arthritis correlated these vitro binding OspA163-175 peptide to 14 DRB molecules. Among patients, were similar those control subjects. However,...
Soluble HLA-DR401 or -DR404 tetramers containing a peptide corresponding to an immunodominant epitope from human GAD65 were used analyze peripheral blood T-cells of newly diagnosed type 1 diabetic patients and at-risk subjects. Peripheral mononuclear cells expanded on antigen-presenting presenting subsequently activated with specific plate-bound class II-peptide monomers. T-cell activation defined in flow cytometry by CD4(high) and/or CD25 markers observed all some subjects, but not normal...
HLA-DR4, Dw4-associated haplotypes associated with IDDM and JRA were compared using genomic DNA restriction fragment analysis to distinguish among DQ beta alpha alleles linked DR4. polymorphisms that subdivide the HLA-DQw3 specificity into DQ3.1 3.2 identified. More than 90% of DR4+ patients express one these alleles, DQ3.2; enzyme mapping indicates presence this allele also accounts for patterns previously reported in IDDM. Furthermore, haplo-identical siblings DQ3.2 carry allele,...
The high concentration of foreign antigen in the lumen gastrointestinal tract is separated from underlying lymphocytes by a single cell layer polarized epithelium. Intestinal epithelial cells can express HLA class II antigens and may function as antigen-presenting to CD4(+) T within intestinal mucosa. Using tetanus toxoid specific HLA-DR-restricted lymphocytes, we show that directed HLA-DR molecules are able initiate processing only after internalization their apical surface. Coexpression...
Abstract Hyaluronan is a glycosaminoglycan present in the extracellular matrix. When hyaluronan degraded during infection and injury, low m.w. forms are generated whose interactions influence inflammation angiogenesis. Intact high hyaluronan, conversely, conveys anti-inflammatory signals. We demonstrate that enhances human CD4+CD25+ regulatory T cell functional suppression of responder proliferation, whereas does not. High also up-regulates transcription factor FOXP3 on cells. These effects...
The HLA association with insulin-dependent diabetes mellitus is highest among individuals heterozygous for DR3 and DR4. To investigate potential mechanisms to account this association, we performed two-dimensional gel-electrophoretic analysis of molecules from DR3/4 patients. These studies demonstrated hybrid molecular dimers corresponding products HLA-DQ genes linked DR4, i.e., the DQw2 DQw3 genes, respectively. Two types OQ were found: immunoprecipitation by DQw3-specific monoclonal...