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Expression of an ovalbumin-specific V{beta}8.2 TCR transgene inhibits collagen arthritis in B10.Q mice 总被引:1,自引:1,他引:0
Nabozny Gerald H.; Rimm Ilonna J.; Griffiths Marie M.; Luthra Harvinder S.; David Chella S. 《International immunology》1995,7(8):1279-1286
Previous studies have illustrated the importance of T cellsbearing ß TCRs in the induction and development ofcollagen induced arthritis (CIA) in mice. However, the scopeof TCR usage in CIA has yet to be clearly defined. Given theinherent diversity of the TCR repertoire, the relative flexibilityof the arthritogenic TCR repertoire specific for type II collagen(CII) is not clear. Therefore, we chose to examine the influenceof a highly skewed TCR repertoire on CIA. Arthritis susceptibleB10.Q (H-2q) mice were mated with C57L (H-2b) animals expressingan ovalbuminspecific Vß8.2 TCR transgene (Tg) andTg+ offspring were further backcrossed to B10.Q. HomozygousH-2a/q, Vß8.2 Tg+ mice displayed a high level of Vß8.2+T cells in peripheral blood. However, expression of some endogenousVß TCR, such as Vß14, was still detected.Upon immunization with bovine CII in adjuvant, Vß8.2Tg+ mice were highly resistant to CIA when compared with Tg–littermates. Analysis of sera demonstrated a marked reductionin antibody specific for homologous mouse CII as well as heterologousbovine CII in Tg+ animals. Interestingly, Vß8.2 Tg+mice still mounted good antibody responses following immunizationwith human thyroglobulin, indicating that the skewed TCR repertoireaffected anti-CII but not antithyroglobulin responses. Thus,our findings show that constraints placed on the TCR repertoireInhibit pathogenic responses against CII and suggest that inH-2q mice the arthritogenlc TCR repertoire bears only limitedflexibility. 相似文献
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Leontiou CA Gueorguiev M van der Spuy J Quinton R Lolli F Hassan S Chahal HS Igreja SC Jordan S Rowe J Stolbrink M Christian HC Wray J Bishop-Bailey D Berney DM Wass JA Popovic V Ribeiro-Oliveira A Gadelha MR Monson JP Akker SA Davis JR Clayton RN Yoshimoto K Iwata T Matsuno A Eguchi K Musat M Flanagan D Peters G Bolger GB Chapple JP Frohman LA Grossman AB Korbonits M 《The Journal of clinical endocrinology and metabolism》2008,93(6):2390-2401
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Alexander Dimitri Miras Anna Kamocka Beln Prez-Pevida Sanjay Purkayastha Krishna Moorthy Ameet Patel Harvinder Chahal Gary Frost Paul Bassett Lidia Castagnetto-Gissey Lucy Coppin Nicola Jackson Anne Margot Umpleby Stephen Robert Bloom Tricia Tan Ahmed Rashid Ahmed Francesco Rubino 《Diabetes care》2021,44(5):1082
OBJECTIVERoux-en-Y gastric bypass (RYGB) characteristically enhances postprandial levels of glucagon-like peptide 1 (GLP-1), a mechanism that contributes to its profound glucose-lowering effects. This enhancement is thought to be triggered by bypass of food to the distal small intestine with higher densities of neuroendocrine L-cells. We hypothesized that if this is the predominant mechanism behind the enhanced secretion of GLP-1, a longer intestinal bypass would potentiate the postprandial peak in GLP-1, translating into higher insulin secretion and, thus, additional improvements in glucose tolerance. To investigate this, we conducted a mechanistic study comparing two variants of RYGB that differ in the length of intestinal bypass.RESEARCH DESIGN AND METHODSA total of 53 patients with type 2 diabetes (T2D) and obesity were randomized to either standard limb RYGB (50-cm biliopancreatic limb) or long limb RYGB (150-cm biliopancreatic limb). They underwent measurements of GLP-1 and insulin secretion following a mixed meal and insulin sensitivity using euglycemic hyperinsulinemic clamps at baseline and 2 weeks and at 20% weight loss after surgery.RESULTSBoth groups exhibited enhancement in postprandial GLP-1 secretion and improvements in glycemia compared with baseline. There were no significant differences in postprandial peak concentrations of GLP-1, time to peak, insulin secretion, and insulin sensitivity.CONCLUSIONSThe findings of this study demonstrate that lengthening of the intestinal bypass in RYGB does not affect GLP-1 secretion. Thus, the characteristic enhancement of GLP-1 response after RYGB might not depend on delivery of nutrients to more distal intestinal segments. 相似文献
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Taneja V Krco CJ Behrens MD Luthra HS Griffiths MM David CS 《Molecular immunology》2007,44(11):2988-2996
Rheumatoid arthritis and its animal model, collagen-induced arthritis, are known as a T and B cell dependent disease. To analyze the role of B cells in arthritis, we generated B cell deficient (microMT) mice carrying HLA-DQ8 as transgene, Abetao.DQ8.micromt mice. HLA-DQ8 transgenic mice (Abetao.DQ8) are susceptible to collagen induced arthritis, an animal model for inflammatory arthritis. Deletion of IgM gene led to the absence of B cells while T cells were comparable to Abetao.DQ8 mice. Arthritis and autoantibodies was completely abrogated in B cell deficient DQ8 mice. T cell response and proinflammatory cytokine production in response to type II collagen and its derived peptides in vitro was significantly decreased despite an increased number of Mac-1 positive cells in DQ8.micromt mice compared to DQ8 mice suggesting B cells could be important for antigen presentation as well. In vitro substitution of B cells from wild type mice restored the response in DQ8.micromt mice. B cells could also present CII-derived peptides to antigen-specific DQ8-restricted hybridomas reinforcing the role of B cells in presentation of antigens to T cells. The data suggest that B cells can be involved in pathogenesis of arthritis by producing autoantibodies and antigen presentation. 相似文献
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Md Jasim Uddin Sumedha Liyanage Noureddine Abidi Harvinder Singh Gill 《Journal of pharmaceutical sciences》2018,107(12):3047-3059
Allergen-free pollen shells obtained from natural pollen grains have recently attracted attention as microcapsules for oral therapeutic delivery. We have recently developed a chemical treatment method that enables successful retrieval of hollow pollen shells from diverse species. A comprehensive characterization is critical to characterize the effects of chemical treatment which will not only benchmark the pollen treatment process but can also lay the foundation of quality control procedures to check allergen-removal efficiency during pollen treatment. Therefore, in this study, we followed the effects of chemical treatment on 4 different pollen species using electron microscopy, elemental analysis, gel electrophoresis, confocal microscopy, Fourier-transform infrared spectroscopy, and thermogravimetric analysis. These analyses revealed that acetone treatment removed lipids from the pollen surface. Phosphoric acid treatment removed proteins and nucleic acids from the pollen core and transformed esters into carboxylic acids. Potassium hydroxide hydrolysis changed carbohydrate composition of the pollen wall. Chemically treated pollen shells exhibited hydroxyl and carboxyl functional groups on their surface. Overall, we propose that confocal microscopy could be used as a rapid scanning technique to visualize the removal of biomolecules, whereas Fourier-transform infrared combined with gel electrophoresis could be used as a more objective approach for analysis and benchmarking. 相似文献
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HSS Journal ® - 相似文献
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HSS Journal ® - Spinal fusion surgery is performed all over the world to help patients with cervical and thoracolumbar pathology. As outcomes continue to improve in patients with spine-related... 相似文献