Gregory G. Burrows

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Autoimmune diseases such as multiple sclerosis (MS) may result from the failure of tolerance mechanisms to prevent expansion of pathogenic T cells. Our study is the first to establish that MS patients have abnormalities in FOXP3 message and protein expression levels in peripheral CD4+ CD25+ T cells (Tregs) that are quantitatively related to a reduction in(More)
Understanding the process of inducing T cell activation has been hampered by the complex interactions between APC and inflammatory Th1 cells. To dissociate Ag-specific signaling through the TCR from costimulatory signaling, rTCR ligands (RTL) containing the alpha1 and beta1 domains of HLA-DR2b (DRA*0101:DRB1*1501) covalently linked with either the myelin(More)
BACKGROUND AND PURPOSE Experimental stroke induces a biphasic effect on the immune response that involves early activation of peripheral leukocytes followed by severe immunodepression and atrophy of the spleen and thymus. In tandem, the developing infarct is exacerbated by influx of numerous inflammatory cell types, including T and B lymphocytes. These(More)
Recombinant T-cell receptor ligands (RTLs) can prevent and reverse clinical and histological signs of experimental autoimmune encephalomyelitis (EAE) in an antigen-specific manner and are currently in clinical trials for treatment of subjects with multiple sclerosis (MS). To evaluate regulatory mechanisms, we designed and tested RTL551, containing the(More)
Major histocompatibility complex (MHC) class II molecules are membrane-anchored heterodimers on the surface of antigen presenting cells (APCs) that bind the T cell receptor, initiating a cascade of interactions that results in antigen-specific activation of clonal populations of T cells. The peptide binding/T cell recognition domains of rat MHC class II(More)
We designed and expressed in bacteria a single-chain two-domain MHC class II molecule capable of binding and forming stable complexes with antigenic peptide. The prototype "beta1alpha1" molecule included the beta1 domain of the rat RT1.B class II molecule covalently linked to the amino terminus of the alpha1 domain. In association with the encephalitogenic(More)
In a previous study, we demonstrated that myelin oligodendrocyte glycoprotein (MOG)-35-55 peptide could induce severe chronic experimental autoimmune encephalomyelitis (EAE) in HLA-DR2(+) transgenic mice lacking all mouse MHC class II genes. We used this model to evaluate clinical efficacy and mechanism of action of a novel recombinant TCR ligand (RTL)(More)
Stroke induces a biphasic effect on the peripheral immune response that involves early activation of peripheral leukocytes followed by severe immunosuppression and atrophy of the spleen. Peripheral immune cells, including T lymphocytes, migrate to the brain and exacerbate the developing infarct. Recombinant T-cell receptor (TCR) Ligand (RTL)551 is designed(More)
The use of HLA class II-transgenic (Tg) mice has facilitated identification of antigenic T cell epitopes that may contribute to inflammation in T cell-mediated diseases such as rheumatoid arthritis and multiple sclerosis (MS). In this study, we compared the encephalitogenic activity of three DR2-restricted myelin determinants [mouse (m) myelin(More)
The verapamil-like arylazide (-)-[3H]azidopamil specifically photoaffinity labeled two low molecular mass polypeptides, with apparent molecular masses of 22 and 27 kDa, in the endoplasmic reticulum of guinea pig liver, kidney, adrenal gland, and lung. It was recently shown that the 22-kDa polypeptide binds the anti-ischemic phenylalkylamine (-)-[3H]emopamil(More)