116 results on '"Rusung Tan"'
Search Results
102. DNA- and MVA-based multi-CTL epitope vaccines for HIV and Plasmodium falciparum: Immunogenicity in mice and macaques
- Author
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Tom Blanchard, A McMichael, Geoffrey L. Smith, Sarah C. Gilbert, A. V. S. Hill, Rusung Tan, T. Hanke, Marion Becker, and Joerg Schneider
- Subjects
Ctl epitope ,biology ,Immunogenicity ,Immunology ,Human immunodeficiency virus (HIV) ,Plasmodium falciparum ,biology.organism_classification ,medicine.disease_cause ,Virology ,chemistry.chemical_compound ,chemistry ,medicine ,Immunology and Allergy ,DNA - Published
- 1997
103. Natural Killer Cells From Children With Type 1 Diabetes Have Defects in NKG2D-Dependent Function and Signaling.
- Author
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Huilian Qin, I-Fang Lee, Panagiotopoulos, Constadina, Xiaoxia Wang, Chu, Alvina D., Utz, Paul J., Priatel, John J., and Rusung Tan
- Subjects
KILLER cells ,DIABETES in children ,MICE ,BLOOD cells ,CYTOKINES ,INTERLEUKIN-2 - Abstract
OBJECTIVE--Natural killer (NK) cells from NOD mice have numeric and functional abnormalities, and restoration of NK cell function prevents autoimmune diabetes in NOD mice. However, little is known about the number and function of NK cells in humans affected by type 1 diabetes. Therefore, we evaluated the phenotype and function of NK cells in a large cohort of type 1 diabetic children. RESEARCH DESIGN AND METHODS--Peripheral blood mononuclear blood cells were obtained from subjects whose duration of disease was between 6 months and 2 years. NK cells were characterized by flow cytometry, enzyme-linked immunosorbent spot assays, and cytotoxicity assays. Signaling through the activating NK cell receptor, NKG2D, was assessed by immunoblotting and reverse-phase phosphoprotein lysate microarray. RESULTS--NK cells from type 1 diabetic subjects were present at reduced cell numbers compared with age-matched, nondiabetic control subjects and had diminished responses to the cytokines interleukin (IL)-2 and IL-15. Analysis before and after IL-2 stimulation revealed that unlike NK cells from nondiabetic control subjects, NK cells from type 1 diabetic subjects failed to downregulate the NKG2D ligands, major histocompatibility complex class I-related chains A and B, upon activation. Moreover, type 1 diabetic NK cells also exhibited decreased NKG2D-dependent cytotoxicity and interferon-γ secretion. Finally, type 1 diabetic NK cells showed clear defects in NKG2D-mediated activation of the phosphoinositide 3-kinase-AKT pathway. CONCLUSIONS--These results are the first to demonstrate that type 1 diabetic subjects have aberrant signaling through the NKG2D receptor and suggest that NK cell dysfunction contributes to the autoimmune pathogenesis of type 1 diabetes. [ABSTRACT FROM AUTHOR]
- Published
- 2011
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104. Identification of Novel HLA-A*0201--Restricted Epitopes in Recent-Onset Type 1 Diabetic Subjects and Antibody-Positive Relatives.
- Author
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Standifer, Nathan E., Qin Ouyang, Panagiotopoulos, Constadina, Verchere, C. Bruce, Rusung Tan, Greenbaum, Carla J., Pihoker, Catherine, and Nepom, Gerald T.
- Subjects
LYMPHOCYTES ,T cells ,PANCREATIC beta cells ,PEPTIDES ,DIABETES - Abstract
Cytotoxic T-lymphocytes (CTLs) are considered to be essential for β-cell destruction in type 1 diabetes. However, few islet-associated peptides have been demonstrated to activate autoreactive CTLs from type 1 diabetic subjects. In an effort to identify novel epitopes, we used matrix-assisted algorithms to predict peptides of glial fibrillary acidic protein (GFAP), prepro-islet amyloid polypeptide (ppIAPP), and islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) that likely bind to HLA-A*0201 with a strong affinity and contain a COOH-terminal proteasomal cleavage site. Seven peptides stabilized HLA-A*0201 expression in binding assays and were used to stimulate peripheral blood mononuclear cells and were evaluated for granzyme B secretion. We found that 5 of 13 type 1 diabetic subjects and 4 of 6 antibody-positive relatives exhibited greater numbers of granzyme B-secreting cells in response to at least one putative epitope compared with healthy control subjects. The most prevalent responses in antibody-positive and type 1 diabetic subjects were to ppIAPP(9-17). Other peptides recognized by type 1 diabetic or antibody-positive subjects included GFAP(143-151), IGRP(152-160), and GFAP(214-222). These data implicate peptides of ppIAPP, GFAP, and IGRP as CTL epitopes for a heterogenous CD8
+ T-cell response in type I subjects and antibody-positive relatives. Diabetes 55:3061-3067, 2006 [ABSTRACT FROM AUTHOR]- Published
- 2006
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105. Recognition of HLA Class I-Restricted β-Cell Epitopes in Type 1 Diabetes.
- Author
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Qin Ouyang, Standifer, Nathan E., Huilian Qin, Gottlieb, Peter, Verchere, C. Bruce, Nepom, Gerald T., Rusung Tan, and Panagiotopoulos, Constadina
- Subjects
DIABETES ,LIVER cells ,PROTEINS ,PEPTIDES ,PEOPLE with diabetes - Abstract
Type 1 diabetes results from the autoimmune destruction of insulin-producing pancreatic β-cells by cytotoxic T-lymphocytes (CTLs). In humans, few β-cell epitopes have been reported, thereby limiting the study of β-cell-specific CTLs in type 1 diabetes. To identify additional epitopes, HLA class I peptide affinity algorithms were used to identify a panel of peptides derived from the β-cell proteins islet amyloid polypeptide (IAPP), islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP), insulin, insulinoma-associated antigen 2 (IA-2), and phogrin that were predicted to bind HLA-A*0201. Peripheral blood mononuclear cells from 24 HLA-A*0201 recent-onset type 1 diabetic patients and 11 nondiabetic control subjects were evaluated for γ-interferon secretion in response to peptide stimulation in enzyme-linked immunospot assays. We identified peptides IAPP9-17, IGRP215-223, IGRP152-160, islet IA-2(172-180), and IA-2(482-490) as novel HLA-A*0201-restricted T-cell epitopes in type 1 diabetic patients. Interestingly, we observed a strong inverse correlation between the binding affinity of β-cell peptides to HLA-A*0201 and CTL responses against those peptides in recent-onset type I diabetic patients. In addition, we found that self-reactive CTLs with specificity for an insulin peptide are frequently present in healthy individuals. These data suggest that many β-cell epitopes are recognized by CTLs in recent-onset type I diabetic patients. These epitopes may be important in the pathogenesis of type 1 diabetes. Diabetes 55:3068-3074, 2006 [ABSTRACT FROM AUTHOR]
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- 2006
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106. Current approaches for the prediction and identification of CD8 T-cell epitopes in type 1 diabetes.
- Author
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Nathan E Standifer, Constadina Panagiotopoulos, and Rusung Tan
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- 2005
107. Chronic Active Epstein-Barr Virus Infection Associated with Low Expression of Leukocyte-Associated Immunoglobulin-like Receptor-1 (LAIR-1) on Natural Killer Cells.
- Author
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Aoukaty, Ala, Lee, I-Fang, Wu, John, and Rusung Tan
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EPSTEIN-Barr virus ,KILLER cells - Abstract
Reports on the case of a patient with chronic active Epstein-Barr virus (CAEBV) infection with defective natural killer (NK) cell function. Decrease in the expression of the inhibitory receptor, leukocyte-associated immunoglobulin-like receptor-1 as shown in the derivation of NK cell from the patient.
- Published
- 2003
108. Antigen–specific release of β-chemokines by anti-HIV-1 cytotoxic T lymphocytes
- Author
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Tao Dong, Rodney E. Phillips, Sarah Rowland-Jones, Rusung Tan, Andrew K. Sewell, Philip J. R. Goulder, and David Price
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Chemokine ,Epitopes, T-Lymphocyte ,Human leukocyte antigen ,Polymerase Chain Reaction ,General Biochemistry, Genetics and Molecular Biology ,Epitope ,03 medical and health sciences ,0302 clinical medicine ,Antigen ,HLA Antigens ,Humans ,Cytotoxic T cell ,Chemokine CCL4 ,Chemokine CCL5 ,Chromatography, High Pressure Liquid ,030304 developmental biology ,0303 health sciences ,biology ,Agricultural and Biological Sciences(all) ,Biochemistry, Genetics and Molecular Biology(all) ,T-cell receptor ,Macrophage Inflammatory Proteins ,Molecular biology ,Beta Chemokine ,3. Good health ,Chemokines, CC ,HIV-1 ,biology.protein ,Peptides ,General Agricultural and Biological Sciences ,CD8 ,T-Lymphocytes, Cytotoxic ,030215 immunology - Abstract
A major advance in understanding human immunodeficiency virus (HIV) biology was the discovery that the β -chemokines MIP-1 α (macrophage inflammatory protein-1 α ), MIP-1 β (macrophage inflammatory protein-1 β ) and RANTES (regulated on activation, normal T-cell expressed and secreted) inhibit entry of HIV-1 into CD4 + cells by blocking the critical interaction between the CCR5 coreceptor and the V3 domain of the viral envelope glycoprotein gp120 [1,2]. CD8 + lymphocytes are a major source of β -chemokines [3], but the stimulus for chemokine release has not been well defined. Here, we have shown that engagement of CD8 + cytotoxic T lymphocytes (CTLs) with HIV-1-encoded human leukocyte antigen (HLA) class I-restricted peptide antigens caused rapid and specific release of these β -chemokines. This release paralleled cytolytic activity and could be attenuated by naturally occurring amino acid variation within the HLA class I-restricted peptide sequence. Epitope variants that bound to appropriate HLA class I molecules but failed to stimulate cytolytic activity in CTLs also failed to stimulate chemokine release. We conclude that signalling through the T-cell receptor (TCR) following binding of antigen results in β -chemokine release from CTLs in addition to cytolytic activity, and that both responses can be abolished by epitope mutation. These results suggest that antigenic variation within HIV-1 might not only allow the host cell to escape lysis, but might also contribute to the propagation of infection by failing to activate β -chemokine-mediated inhibition of HIV-1 entry.
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109. A phase 1b open-label dose-finding study of ustekinumab in young adults with type 1 diabetes
- Author
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Evangelia Williams, Megan K. Levings, Tom Elliott, Anne M. Pesenacker, Timothy Tree, Kristina M Harris, Jan P. Dutz, Clara Domingo-Vila, Annika Sun, Khalif Halani, S. Alice Long, Laura Cook, Rusung Tan, Samuel Chow, Jennie H M Yang, Kirsten A. Ward-Hartstonge, and Ashish Marwaha
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Type 1 diabetes ,Pediatrics ,medicine.medical_specialty ,type 1 diabetes ,business.industry ,AcademicSubjects/MED00730 ,clinical trial ,General Medicine ,medicine.disease ,ustekinumab ,Dose finding ,Ustekinumab ,medicine ,Young adult ,Open label ,business ,immunomodulatory ,Research Article ,medicine.drug - Abstract
Summary Objectives We assessed the safety of ustekinumab (a monoclonal antibody used in psoriasis to target the IL-12 and IL-23 pathways) in a small cohort of recent-onset (, Graphical Abstract
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110. T-cell epitopes in type 1 diabetes
- Author
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Constadina Panagiotopoulos, Jacqueline D. Trudeau, and Rusung Tan
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CD4-Positive T-Lymphocytes ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,T-Lymphocytes ,Population ,Context (language use) ,Autoimmunity ,Nod ,Biology ,CD8-Positive T-Lymphocytes ,medicine.disease_cause ,Lymphocyte Activation ,Autoantigens ,Epitope ,Epitopes ,Islets of Langerhans ,Mice ,Mice, Inbred NOD ,Internal Medicine ,medicine ,Cytotoxic T cell ,Animals ,Humans ,Insulin ,education ,education.field_of_study ,Histocompatibility Antigens Class I ,Immunotherapy ,Diabetes Mellitus, Type 1 ,Immunology ,CD8 - Abstract
Type 1 diabetes (TID) results from T-cell-mediated destruction of pancreatic b cells in genetically predisposed individuals. Autoreactive CD4(+) T helper cells and CD8(+) cytotoxic T lymphocytes (CTLs) recognize b-cell-derived peptides in the context of major histocompatibility complex class II and I molecules, respectively, in a process that terminates in b-cell death. Many peptide epitopes derived from b-cell proteins have been described for both humans and the nonobese diabetic (NOD) mouse, but their relative importance in disease pathogenesis is unclear. The significance of identifying key b-cell epitopes is underscored by a study showing that in the NOD mouse monitoring of a single population of b-cell-specific CTLs in the peripheral blood using a high-avidity analogue of the endogenous peptide may be used to accurately predict diabetes occurrence. Future studies focused on the discovery of immunodominant b-cell epitopes and their high-avidity analogues should have considerable implications for prediction and immunotherapy of TID.
111. Evaluation of a diagnostic polymerase chain reaction assay for Neisseria meningitidis in North America and field experience during an outbreak
- Author
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Pollard, A. J., Probe, G., Trombley, C., Castell, A., Whitehead, S., Bigham, J. M., Champagne, S., Isaac-Renton, J., Rusung Tan, Guiver, M., Borrow, R., Speert, D. P., and Thomas, E.
- Abstract
CONTEXT: Meningococcal infection has a high public profile because of its dramatic presentation, high fatality rate, and propensity to occur in outbreaks and clusters of cases. Use of a diagnostic polymerase chain reaction (PCR) assay could enhance laboratory confirmation of cases and guide the public health response in North America. OBJECTIVE: To assess the performance of a PCR assay for the diagnosis of meningococcal disease after its implementation in a North American setting and to evaluate sensitivity and specificity of the assay for the detection of prevalent bacterial isolates. DESIGN: Laboratory evaluation of the sensitivity and specificity of a PCR assay for Neisseria meningitidis and observational study of a series of cases comparing molecular diagnosis against the criterion standard of conventional laboratory diagnostic tests. SETTING: A Canadian province with a population of 4 million people. PATIENTS: Children and adults presenting with suspected meningococcal disease in British Columbia. MAIN OUTCOME MEASURES: The sensitivity and specificity of the PCR assay when compared against standard laboratory methods. RESULTS: The PCR assay correctly identified all of 38 Canadian isolates of Neisseria meningitidis and correctly assigned the serogroup to each isolate. None of 57 other gram-positive or gram-negative bacteria or yeasts were detected by the PCR assay. In a clinical evaluation, for diagnosis of meningococcal disease, the PCR assay had a sensitivity and specificity of 91% and 76%, respectively, against conventional methods of diagnosis. Use of the PCR assay increased the laboratory confirmation of clinically suspected cases by 36%. During an outbreak, the PCR assay allowed serogroup determination in 3 of 7 cases, aiding in the public health decision to launch an immunization campaign. CONCLUSIONS: The PCR assay is more sensitive than conventional methods for the diagnosis of meningococcal disease, and enhanced surveillance may help direct the public health response to the changing epidemiology of disease in North America.
112. Role of cellular immunity in protection against HIV infection
- Author
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Rowland-Jones, S., Rusung Tan, and Mcmichael, A.
113. T regulatory cell chemokine production mediates pathogenic T cell attraction and suppression.
- Author
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Patterson, Scott J., Pesenacker, Anne M., Wang, Adele Y., Gillies, Jana, Mojibian, Majid, Morishita, Kim, Rusung Tan, Kieffer, Timothy J., Verchere, C. Bruce, Panagiotopoulos, Constadina, Levings, Megan K., and Tan, Rusung
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T cells , *CHEMOKINES , *IMMUNOREGULATION , *GENE expression , *ANTIGENS , *LABORATORY mice , *PHYSIOLOGY , *CELL receptors , *ANIMAL experimentation , *CELL culture , *CELL physiology , *CYTOKINES , *DEMYELINATION , *DIABETES , *IMMUNIZATION , *TYPE 1 diabetes , *MICE , *RESEARCH funding , *THERAPEUTICS - Abstract
T regulatory cells (Tregs) control immune homeostasis by preventing inappropriate responses to self and nonharmful foreign antigens. Tregs use multiple mechanisms to control immune responses, all of which require these cells to be near their targets of suppression; however, it is not known how Treg-to-target proximity is controlled. Here, we found that Tregs attract CD4+ and CD8+ T cells by producing chemokines. Specifically, Tregs produced both CCL3 and CCL4 in response to stimulation, and production of these chemokines was critical for migration of target T cells, as Tregs from Ccl3-/- mice, which are also deficient for CCL4 production, did not promote migration. Moreover, CCR5 expression by target T cells was required for migration of these cells to supernatants conditioned by Tregs. Tregs deficient for expression of CCL3 and CCL4 were impaired in their ability to suppress experimental autoimmune encephalomyelitis or islet allograft rejection in murine models. Moreover, Tregs from subjects with established type 1 diabetes were impaired in their ability to produce CCL3 and CCL4. Together, these results demonstrate a previously unappreciated facet of Treg function and suggest that chemokine secretion by Tregs is a fundamental aspect of their therapeutic effect in autoimmunity and transplantation. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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114. SLAM-SAP Signaling Promotes Differentiation of IL-17-Producing T Cells and Progression of Experimental Autoimmune Encephalomyelitis.
- Author
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Yu-Hsuan Huang, Kevin Tsai, Caixia Ma, Vallance, Bruce A., Priatel, John J., and Rusung Tan
- Subjects
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MYCOSES , *ENCEPHALOMYELITIS , *ENCEPHALITIS , *CENTRAL nervous system diseases - Abstract
IL-17 plays critical roles in host defenses, combating bacterial and fungal infections, as well as the pathogenesis of autoimmune diseases such as experimental autoimmune encephalomyelitis (EAE). The signaling adaptor SAP is essential for normal immune homeostasis and mutations within SH2D1A, the locus encoding this protein, result in serious and sometimes fatal syndromes, including X-linked lymphoproliferative disease and severe cases of common variable immunodeficiency. However, the precise cellular basis of how SAP deficiency contributes to immune dysfunction remains incompletely understood. In this study, we found that CD4 and CD8 T cells lacking SAP had a diminished capacity to differentiate into IL-17-producing Th17 and T cytotoxic (Tc17) cells relative to wild-type lymphocytes. The use of costimulating SLAM Abs was found to augment the differentiation of IL-17-secreting effectors in wild-type but not Sh2d1a-/- splenic T cells under IL-17-polarizing conditions. In addition, SAP's regulation of IL-17-secreting T cells was shown to be a T cell-intrinsic role, as purified naive Sh2d1a-/- CD4 and CD8 T cells were inherently defective at converting into Th17 and Tc17 cells in vitro and in vivo. Furthermore, Sh2d1a-/- mice were protected from EAE and exhibited greatly decreased numbers of CNS-infiltrating Th17 and Tc17 effector T cells and reduced disease severity. Collectively, these results suggest that SLAM-SAP signaling drives the differentiation and function of Th17 and Tc17 cells in vitro and in vivo and contributes to the pathogenesis of autoimmunity in EAE. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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115. Innate immune control of EBV-infected B cells by invariant natural killer T cells.
- Author
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Chung, Brian K., Tsai, Kevin, Allan, Lenka L., Dong Jun Zheng, Nie, Johnny C., Biggs, Catherine M., Hasan, Mohammad R., Kozak, Frederick K., van den Elzen, Peter, Priatel, John J., and Rusung Tan
- Subjects
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NATURAL immunity , *EPSTEIN-Barr virus diseases , *B cells , *T cells , *LYMPHOBLASTOID cell lines , *NUCLEAR proteins , *CELL-mediated cytotoxicity - Abstract
Individuals with X-linked lymphoproliferative disease lack invariant natural killer T (iNKT) cells and are exquisitely susceptible to Epstein-Barr virus (EBV) infection. To determine whether iNKT cells recognize or regulate EBV, resting B cells were infected with EBV in the presence or absence of iNKT cells. The depletion of iNKT cells increased both viral titers and the frequency of EBV-infected B cells. However, EBV-infected B cells rapidly lost expression of the iNKT cell receptor ligand CD1d, abrogating iNKT cell recognition. To determine whether induced CD1d expression could restore iNKT recognition in EBV-infected cells, lymphoblastoid cell lines (LCL) were treated with AM580, a synthetic retinoic acid receptor-a agonist that upregulates CD1d expression via the nuclear protein, lymphoid enhancer-binding factor 1 (LEF-1). AM580 significantly reduced LEF-1 association at the CD1d promoter region, induced CD1d expression on LCL, and restored iNKT recognition of LCL. CD1d-expressing LCL elicited interferon γ secretion and cytotoxicity by iNKT cells even in the absence of exogenous antigen, suggesting an endogenous iNKT antigen is expressed during EBV infection. These data indicate that iNKT cells may be important for early, innate control of B cell infection by EBV and that downregulation of CD1d may allow EBV to circumvent iNKT cell-mediated immune recognition. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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116. Prediction of spontaneous autoimmune diabetes in NOD mice by quantification of autoreactive T cells in peripheral blood.
- Author
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Trudeau, Jacqueline D., Kelly-Smith, Carolyn, Verchere, C. Bruce, Elliott, John F., Dutz, Jan P., Finegood, Diane T., Santamaria, Pere, and Rusung Tan
- Subjects
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DIABETES , *T cells , *BLOOD - Abstract
Presents a study on the prediction of spontaneous autoimmune diabetes in NOD mice by quantification of autoreactive T cells in peripheral blood. Background on Type I diabetes; Methodology; Results of the study.
- Published
- 2003
- Full Text
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