Maki Nakayama

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Regulatory T cells (T(reg) cells) are central to the maintenance of immune homeostasis. However, little is known about the stability of T(reg) cells in vivo. In this study, we demonstrate that a substantial percentage of cells had transient or unstable expression of the transcription factor Foxp3. These 'exFoxp3' T cells had an activated-memory T cell(More)
A fundamental question about the pathogenesis of spontaneous autoimmune diabetes is whether there are primary autoantigens. For type 1 diabetes it is clear that multiple islet molecules are the target of autoimmunity in man and animal models. It is not clear whether any of the target molecules are essential for the destruction of islet beta cells. Here we(More)
Regulation of metabolic pathways in the immune system provides a mechanism to actively control cellular function, growth, proliferation, and survival. Here, we report that miR-181 is a nonredundant determinant of cellular metabolism and is essential for supporting the biosynthetic demands of early NKT cell development. As a result, miR-181-deficient mice(More)
In the nonobese diabetic (NOD) mouse model of type 1 diabetes (T1D), an insulin peptide (B:9-23) is a major target for pathogenic CD4(+) T cells. However, there is no consensus on the relative importance of the various positions or "registers" this peptide can take when bound in the groove of the NOD MHCII molecule, IA(g7). This has hindered structural(More)
Although multiple islet autoantigens are recognized by T lymphocytes and autoantibodies before the development of type 1A (immune-mediated diabetes), there is increasing evidence that autoimmunity to insulin may be central to disease pathogenesis. Evidence is strongest for the NOD mouse model where blocking immune responses to insulin prevents diabetes, and(More)
OBJECTIVE To investigate the prevalence of beta-cell autoantigen-reactive peripheral T-cells in type 1 diabetes, we developed an immunoglobulin-free enzyme-linked immunospot (ELISPOT) assay and assessed its usefulness for diagnosing this disease. RESEARCH DESIGN AND METHODS Cellular immune responses to beta -cell autoantigens were studied both by(More)
A series of recent studies in humans and the NOD mouse model have highlighted the central role that autoimmunity directed against insulin, in particular the insulin B chain 9-23 peptide, may play in the pathogenesis of type 1 diabetes. Both pathogenic and protective T-cell clones recognizing the B:9-23 peptide have been produced. This report describes the(More)
OBJECTIVE The objective of this study was to define the spectrum of TCR beta chains permissive for T cells with alpha chains containing the conserved TRAV5D-4*04 sequence to target the insulin B:9-23 peptide, a major epitope for initiation of diabetes in the NOD mouse. MATERIALS AND METHODS We produced T cell hybridomas from mice with single T cell(More)
We generated a novel nonpeptidic protease inhibitor (PI), GRL-02031, by incorporating a stereochemically defined fused cyclopentanyltetrahydrofuran (Cp-THF) which exerted potent activity against a wide spectrum of human immunodeficiency virus type 1 (HIV-1) isolates, including multidrug-resistant HIV-1 variants. GRL-02031 was highly potent against(More)
Certain class II MHC (MHCII) alleles in mice and humans confer risk for or protection from type 1 diabetes (T1D). Insulin is a major autoantigen in T1D, but how its peptides are presented to CD4 T cells by MHCII risk alleles has been controversial. In the mouse model of T1D, CD4 T cells respond to insulin B-chain peptide (B:9-23) mimotopes engineered to(More)