CD8 cytotoxic T-cell clone rapidly transfers autoimmune diabetes in very young NOD and MHC class I-compatible scid mice

Yoneda, Ryoji; Yokono, Koichi; Nagata, Michio; Tominaga, Yoshihiro; Moriyama, Hiroaki; Tsukamoto, Kazuya; Miki, Masaki; Okamoto, Nobuhiko; Yasuda, Hisafumi; Amano, Kazutaka; Kasuga, Masato

doi:10.1007/s001250050786

Cited by 24 publications

(11 citation statements)

References 27 publications

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“…As we and others have previously reported, CD8 ϩ effector T-cells induce overt diabetes without the help of CD4 ϩ T-cells (17,21). These results indicated that Fas/FasLmediated cytolysis was not responsible for the CD8 ϩ T-cell-mediated ␤-cell destruction.…”

Section: Discussionsupporting

confidence: 69%

“…ϩ T-cells (CD8 ϩ CTL [cytotoxic T lymphocytes]) were generated from lymphocytes infiltrating islets in 20-week-old female NOD mice (17). Isolated islets containing infiltrating lymphocytes were cultured in RPMI 1640 medium supplemented with 10% FCS and 3 U/ml recombinant interleukin-2 (rIL-2) (Takeda Pharmaceutical, Osaka, Japan) in a humidified incubator at 37°C.…”

Section: Cells Islet-derived Cd8mentioning

confidence: 99%

“…ϩ CTL-induced diabetes develops very rapidly (17), and 4 weeks after transfer of YNK7.3. Paraffin-embedded sections were stained with hematoxylin and eosin and scored for insulitis using the following criteria: 0 (-), no cellular infiltration; 1 (Ϯ), periinsulitis; 2 (ϩ), intraislet infiltration in Ͻ25% of islets; 3 (ϩϩ), 25-50% intraislet infiltration; 4 (ϩϩϩ), Ͼ50% intraislet infiltration.…”

Section: Cells Islet-derived Cd8mentioning

confidence: 99%

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Fas/Fas Ligand Interactions Play an Essential Role in the Initiation of Murine Autoimmune Diabetes

et al. 2002

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These results suggest a substantial contribution of Fas/ FasL interactions to CD4؉ , but not CD8 ؉ , T-cell-mediated destruction of pancreatic ␤-cells. When anti-FasL antibody was administered to NOD mice between 5 and 15 weeks of age, the onset of diabetes was slightly delayed but the incidence was not decreased. However, administration of anti-FasL antibody at 2-4 weeks of age completely prevented insulitis and diabetes. These results suggest that Fas/FasL interactions contribute to CD4 ؉ T-cell-mediated ␤-cell destruction and play an essential role in the initiation of autoimmune NOD diabetes.

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Section: Discussionsupporting

confidence: 69%

Section: Cells Islet-derived Cd8mentioning

confidence: 99%

Section: Cells Islet-derived Cd8mentioning

confidence: 99%

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Fas/Fas Ligand Interactions Play an Essential Role in the Initiation of Murine Autoimmune Diabetes

et al. 2002

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“…Activated CD8-positive CTLs play a rate-limiting role in the onset and early progression of insulin-dependent diabetes mellitus (IDDM) by targeting and destroying the insulin-producing β-islet cells of the pancreas [1][2][3][4][5][6] . In addition to their role in autoimmunity, activated CTLs are known to aid in the rejection processes associated with solid organ transplantation 7 and in Graft versus Host Disease 8 .…”

Section: Research Articlesmentioning

confidence: 99%

Rational design of cytotoxic T-cell inhibitors

et al. 2000

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This study describes the use of the CD8/major histocompatibility complex (MHC) class I crystal structure as a template for the de novo design of low-molecular-weight surface mimetics. The analogs were designed from a local surface region on the CD8 alpha-chain directly adjacent to the bound MHC class I, to block the protein associations in the T-cell activation cluster that occur upon stimulation of the cytotoxic T lymphocytes (CTLs). One small conformationally restrained peptide showed dose-dependent inhibition of a primary allogeneic CTL assay while having no effect on the CD4-dependent mixed lymphocyte reaction (MLR). The analog's activity could be modulated through subtle changes in its side chain composition. Administration of the analog prevented CD8-dependent clearance of a murine retrovirus in BALB/c mice. In C57BL/6 mice challenged with the same retrovirus, the analog selectively inhibited the antiviral CTL responses without affecting the ability of the CTLs to generate robust allogeneic responses.

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“…Based on evidence from homing of CD8 ϩ T cell clones to the lung (11), islets of Langerhans (12), internal elastic lamina and lamina propria of the gut (13), and other inflamed tissues, it is clear that lymphocyte activation is required for recruitment of effector T cells. The sequence of events required is thought to encompass rolling, activation, arrest, and transmigration, akin to the paradigm known for neutrophil recruitment (10).…”

mentioning

confidence: 99%

A CD2-Green Fluorescence Protein-Transgenic Mouse Reveals Very Late Antigen-4-Dependent CD8+ Lymphocyte Rolling in Inflamed Venules

Singbartl

Thatte

Smith

et al. 2001

The Journal of Immunology

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Intravital microscopy allows detailed analysis of leukocyte trafficking in vivo, but fails to identify the nature of leukocytes investigated. Here, we describe the development of a CD2-enhanced green fluorescence protein (EGFP)-transgenic mouse to characterize lymphocyte trafficking during inflammation in vivo. A CD2-EGFP plasmid construct including the CD2 promoter, the EGFP transgene, and the CD2 locus control region was injected into B6CBA/F1 pronuclei. EGFP+ offspring were backcrossed into C57BL/6 mice for six generations. Flow cytometry demonstrated that all peripheral blood EGFP+ cells were positive for CD2 and negative for the granulocyte Ag Ly 6-G (GR-1). EGFPhigh cells stained positive for CD2, CD3, CD8, TCR β-chain, and NK1.1 but did not express the B cell and monocyte markers CD45RA, CD19, and CD11b. In vitro stimulation assays revealed no difference in lymphocyte proliferation and IL-2 secretion between EGFP+ and EGFP− mice. Intravital microscopy of untreated or TNF-α-treated cremaster muscle venules showed EGFP+ cells in vivo, but these cells did not roll or adhere to the vessel wall. In cremaster muscle venules treated with both TNF-α and IFN-γ, EGFPhigh cells rolled, adhered, and transmigrated at a rolling velocity slightly higher (11 μm/s) than that of neutrophils (10 μm/s). Blocking α4 integrin with a mAb increased rolling velocity to 24 μm/s. These findings show that CD8+ T cells roll in TNF-α/IFN-γ-pretreated vessels in vivo via an α4 integrin-dependent pathway.

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CD8 cytotoxic T-cell clone rapidly transfers autoimmune diabetes in very young NOD and MHC class I-compatible scid mice

Cited by 24 publications

References 27 publications

Fas/Fas Ligand Interactions Play an Essential Role in the Initiation of Murine Autoimmune Diabetes

Fas/Fas Ligand Interactions Play an Essential Role in the Initiation of Murine Autoimmune Diabetes

Rational design of cytotoxic T-cell inhibitors

A CD2-Green Fluorescence Protein-Transgenic Mouse Reveals Very Late Antigen-4-Dependent CD8+ Lymphocyte Rolling in Inflamed Venules

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