Surge in regulatory T cells does not prevent onset of hyperglycemia in NOD mice: immune profiles do not correlate with disease severity.


:Immune profiling of non-obese diabetic (NOD) is a widely employed tool to assess the mechanisms of inflammatory insulitis. Our analysis of the female NOD colony revealed similar distribution of lymphoid lineages to wild type mice, and at various ages of prediabetic and diabetic mice. The profiles of mesenteric and pancreatic lymph nodes differ and often change reciprocally due to directed migration of T cells towards the site of inflammation. Significant events in our colony include early decline in CD4(+)CD25(+)CD62L(+) Treg, accompanied by gradual increase in CD4(+)CD25(+)FoxP3(+) Treg in peripheral lymphoid organs and pancreatic infiltrates. Impressively, aged euglycemic mice display significant transient rise in CD4(+)CD25(-)FoxP3(+) Treg in the thymus, pancreas and draining lymph nodes. A significant difference was superior viability of effector and suppressor cells from new onset diabetics in the presence of high interleukin-2 (IL-2) concentrations in vitro as compared to cells of prediabetic mice. Overall, we found no correlation between FoxP3(+) Treg in the pancreatic lymph nodes and the inflammatory scores of individual NOD mice. CD25(-)FoxP3(+) Treg are markedly increased in the pancreatic infiltrates in late stages of inflammation, possibly an effort to counteract destructive insulitis. Considering extensive evidence that Treg in aged NOD mice are functionally sufficient, quantitative profiling evolves as an unreliable tool to assess mechanism and causes of inflammation under baseline conditions. Immune profiles are modulated by thymic output, cell migration, shedding of markers, proliferation, survival and in-situ evolution of regulatory cells.






Kaminitz A,Mizrahi K,Askenasy N




Has Abstract


2014-03-01 00:00:00












  • Antibodies to the protein tyrosine phosphatases IAR and IA-2 are associated with progression to insulin-dependent diabetes (IDDM) in first-degree relatives at-risk for IDDM.

    abstract::Insulin-dependent diabetes mellitus (IDDM) is preceded by the presence of antibodies against islet proteins including a protein tyrosine phosphatase (PTP) designated IA-2. Recently, we cloned a novel PTP named IAR which shares 43% sequence identity with IA-2 and is recognised by antibodies from a majority of patients ...


    pub_type: 杂志文章


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  • Immune-mediated mechanisms of endothelial damage in atherosclerosis.

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    pub_type: 杂志文章,评审


    authors: Foteinos G,Xu Q

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  • Immunoreactivity to various human cytochrome P450 proteins of sera from patients with autoimmune hepatitis, chronic hepatitis B, and chronic hepatitis C.

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    pub_type: 杂志文章


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    pub_type: 杂志文章


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    authors: Peng B,Yoshitoshi T,Shichi H

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  • Functional implications of IgG anti-endothelial cell antibodies in pulmonary arterial hypertension.

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    pub_type: 杂志文章,评审


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    pub_type: 杂志文章


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  • Islet protein expression changes during diabetes development in islet syngrafts in BB-DP rats and during rejection of BB-DP islet allografts.

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    pub_type: 杂志文章


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    pub_type: 杂志文章,评审


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  • PD-1/PD-L pathway and autoimmunity.

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    pub_type: 杂志文章,评审


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    pub_type: 杂志文章


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    pub_type: 杂志文章


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    pub_type: 杂志文章


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    pub_type: 杂志文章


    authors: Lucke S,Klöting I,Pusch A,Heinrich HW,Hahn HJ

    更新日期:2003-05-01 00:00:00

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    pub_type: 杂志文章


    authors: Mattecka S,Bock C,Vogt B,Yapici G,Schrödl W,Janko C,Schindler R,Sheriff A

    更新日期:2013-08-01 00:00:00

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    pub_type: 社论


    authors: Perl A

    更新日期:2010-02-01 00:00:00

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    pub_type: 杂志文章


    authors: Haas JP,Metzler M,Frank C,Haefner R,Wassmuth R

    更新日期:2009-05-01 00:00:00

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    pub_type: 杂志文章


    authors: Loeffler DA,Klaver AC,Coffey MP

    更新日期:2015-06-01 00:00:00

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    pub_type: 杂志文章,评审


    authors: Kahaly G,Stover C,Otto E,Beyer J,Schuler M

    更新日期:1992-01-01 00:00:00