Prevention of autoimmune insulitis in nonobese diabetic mice by expression of major histocompatibility complex class I Ld molecules.

Miyazaki, Toru; Matsuda, Yoichi; Toyonaga, Tetsushi; Miyazaki, Jun; Yazaki, Yoshio; Yamamura, Ken Ichi

doi:10.1073/pnas.89.20.9519

Cited by 29 publications

(11 citation statements)

References 59 publications

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“…Our data suggest that allelic polymorphisms of class I K and/or D genes may be one of the mechanisms in the reduction of the incidence of IDDM in NOD.CTS-H-2 congenic mice. Consistent with this, suppression of insulitis was reported in transgenic NOD mice expressing Ld gene ( 15). Transgenic expression of NOD alleles of class I molecules (Kd and/or Db) in NOD.CTS-H-2 congenic mice would clarify the contribution of class I gene polymorphisms to IDDM susceptibility.…”

Section: Discussionsupporting

confidence: 70%

Identification of a new susceptibility locus for insulin-dependent diabetes mellitus by ancestral haplotype congenic mapping.

Ikegami¹,

Makino²,

Yamato³

et al. 1995

J. Clin. Invest.

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Section: Discussionsupporting

confidence: 70%

Identification of a new susceptibility locus for insulin-dependent diabetes mellitus by ancestral haplotype congenic mapping.

Ikegami¹,

Makino²,

Yamato³

et al. 1995

J. Clin. Invest.

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“…However, we could not discriminate the role of K k and D k expressed in T cells of AKR origin in the reconstituted NOD.scid-RIP-B7.1 mice. The mechanisms of T1D prevention by MHC class I genes of k haplotype expressed in T cells remain unclear, although a previous study suggested regulatory mechanisms induced by the expression of a T1D-resistant class I gene (40). Indeed, the development of regulatory NKT cells requires expression of MHC-I-like CD1d/␤ 2 m complex on the surface of double-positive thymocytes (41) that were mostly donor origin in the reconstituted mice.…”

Section: Discussionmentioning

confidence: 99%

Diabetes Resistance/Susceptibility in T Cells of Nonobese Diabetic Mice Conferred by MHC and MHC-Linked Genes

Ueno

Cho

et al. 2005

The Journal of Immunology

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Polymorphism of MHC and MHC-linked genes is tightly associated with susceptibility to type 1 diabetes (T1D) in human and animal models. Despite the extensive studies, however, the role of MHC and MHC-linked genes expressed by T cells on T1D susceptibility remains unclear. Because T cells develop from TCR− thymic precursor (pre-T) cells that undergo MHC restriction mediated by thymic stroma cells, we reconstituted the T cell compartment of NOD.scid-RIP-B7.1 mice using pre-T cells isolated from NOD, NOR, AKR, and C57BL/6 (B6) mice. T1D developed rapidly in the mice reconstituted with pre-T cells derived from NOD or NOR donors. In contrast, most of the NOD.scid-RIP-B7.1 mice reconstituted with pre-T cells from AKR or B6 donors were free of T1D. Further analysis revealed that genes within MHC locus of AKR or B6 origin reduced incidence of T1D in the reconstituted NOD.scid-RIP-B7.1 mice. The expression of MHC class I genes of k, but not b haplotype, in T cells conferred T1D resistance. Replacement of an interval near the distal end of the D region in T cells of B6 origin with an identical allele of 129.S6 origin resulted in T1D development in the reconstituted mice. These results provide evidence that the expression of MHC class I and MHC-linked genes in T cells of NOD mice indeed contributes to T1D susceptibility, while expression of specific resistance alleles of MHC or MHC-linked genes in T cells alone would effectively reduce or even prevent T1D.

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“…All animal procedures were done in accordance with the guidelines of the Animal Care and Use Committee of the Jackson Laboratory and the University of Massachusetts Medical School and conformed to the recommendations in the Guide for the Care and Use of Laboratory Animals (National Institutes of Health, Bethesda, MD, USA). Supplemental Figure S1 and Supplemental Table S1 provide a direct comparison of the relevant strains used for experiments (28,29,(33)(34)(35)(36).…”

Section: Micementioning

confidence: 99%

Lack of acute xenogeneic graft‐versus‐host disease, but retention of T‐cell function following engraftment of human peripheral blood mononuclear cells in NSG mice deficient in MHC class I and II expression

et al. 2018

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Immunodeficient mice engrafted with human peripheral blood mononuclear cells (PBMCs) support preclinical studies of human pathogens, allograft rejection, and human T‐cell function. However, a major limitation of PBMC engraftment is development of acute xenogeneic graft‐versus‐host disease (GVHD) due to human T‐cell recognition of murine major histocompatibility complex (MHC). To address this, we created 2 NOD‐scid IL‐2 receptor subunit γ (IL2rg)null (NSG) strains that lack murine MHC class I and II [NSG–β‐2‐microglobulin (B2M)null (IA IE)null and NSG‐(Kb Db)null (IAnull)]. We observed rapid human IgG clearance in NSG‐B2Mnull (IA IE)null mice whereas clearance in NSG‐(Kb Db)null (IAnull) mice and NSG mice was comparable. Injection of human PBMCs into both strains enabled long‐term engraftment of human CD4+ and CD8+ T cells without acute GVHD. Engrafted human T‐cell function was documented by rejection of human islet allografts. Administration of human IL‐2 to NSG‐(Kb Db)null (IAnull) mice via adeno‐associated virus vector increased human CD45+ cell engraftment, including an increase in human regulatory T cells. However, high IL‐2 levels also induced the development of GVHD. These data document that NSG mice deficient in murine MHC support studies of human immunity in the absence of acute GVHD and enable evaluation of human antibody therapeutics targeting human T cells.—Brehm, M. A., Kenney, L. L., Wiles, M. V., Low, B. E., Tisch, R. M., Burzenski, L., Mueller, C., Greiner, D. L., Shultz, L. D. Lack of acute xenogeneic graft‐versus‐host disease, but retention of T‐cell function following engraftment of human peripheral blood mononuclear cells in NSG mice deficient in MHC class I and II expression. FASEB J. 33, 3137–3151 (2019). http://www.fasebj.org

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Prevention of autoimmune insulitis in nonobese diabetic mice by expression of major histocompatibility complex class I Ld molecules.

Abstract: Nonobese diabetic (NOD) mice spontaneously develop a T-cefl-mediated autoimmune disease that is similar in many respects to insulin-dependent diabetes mellitus in hu-

Cited by 29 publications

References 59 publications

Identification of a new susceptibility locus for insulin-dependent diabetes mellitus by ancestral haplotype congenic mapping.

Identification of a new susceptibility locus for insulin-dependent diabetes mellitus by ancestral haplotype congenic mapping.

Diabetes Resistance/Susceptibility in T Cells of Nonobese Diabetic Mice Conferred by MHC and MHC-Linked Genes

Lack of acute xenogeneic graft‐versus‐host disease, but retention of T‐cell function following engraftment of human peripheral blood mononuclear cells in NSG mice deficient in MHC class I and II expression

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