Limited effect of CpG ODN in preventing type 1 diabetes in NOD mice

Byong Jun Lee, Soo Kie Kim, Moon Kyu Kim, Eon Sub Park, Hyun Chul Cho, Myung Sook Shim, Mi Jin Kim, Young Goo Shin, Choon Hee Chung

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Type 1 diabetes is considered as Th1 cell mediated autoimmune disease and the suppression of Th1 cells or the activation of Th2 cells has been regarded as a plausible immunologic intervention for the prevention of type 1 diabetogenesis in a rodent model. CpG ODN is an immunostimulatory sequence primarily present in bacterial DNA, viral DNA and BCG. CpG ODN is conventionally classified as a Th1 cell activator, which has been clinically applied to cancer, allergy and infectious disease. Recently, there was a promising report of that CpG ODN administration suppressed the development of type 1 diabetes in NOD mice by inducing Th2 cell mediated cytokine. However, the antidiabetogenic effect of CpG ODN on NOD mice is controversial. Thus, two studies were serially undertaken with various kinds of CpG motif to find a more optimal sequence and administration method. In the first study, CpG ODN was vaccinated four times and pancreatic inflammation and the quantity of serum insulin subsequently evaluated. In the second study, the amounts of IFN γ and IL-4 in sera were measured as representative cytokines of Th1 and Th2 cells, respectively. As a result, vaccination or continuous injection of CpG ODN failed to show a preventive effect on type 1 diabetogenesis in NOD mice. Structural differences of CpG ODN also had no affect on the result. CpG ODN also consistently showed affect on the pancreatic pathology. The productions of IFN γ and IL-4 were detected only in the K and D type CpG ODN administration groups. Comparison of the two cytokines leads to the conclusion that CpG ODN generated a Th1-weighted response in both study groups. It was assumed that CpG ODN failed to produce Th2-weighted cytokine milieu, which can overcome the genetically determined phenotype of NOD mice. Given these results, it was concluded that the immunotherapeutic application of CpG ODN on Type 1 diabetes had clear limitations.

Original languageEnglish
Pages (from-to)341-346
Number of pages6
JournalYonsei medical journal
Volume46
Issue number3
DOIs
Publication statusPublished - 2005 Jun 30

Fingerprint

Inbred NOD Mouse
Th1 Cells
Type 1 Diabetes Mellitus
Th2 Cells
Cytokines
Interleukin-4
Bacterial DNA
Viral DNA
Mycobacterium bovis
Serum
Autoimmune Diseases
Communicable Diseases
Rodentia
Hypersensitivity
Vaccination
Insulin
Pathology
Inflammation
Phenotype
Injections

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Lee, Byong Jun ; Kim, Soo Kie ; Kim, Moon Kyu ; Park, Eon Sub ; Cho, Hyun Chul ; Shim, Myung Sook ; Kim, Mi Jin ; Shin, Young Goo ; Chung, Choon Hee. / Limited effect of CpG ODN in preventing type 1 diabetes in NOD mice. In: Yonsei medical journal. 2005 ; Vol. 46, No. 3. pp. 341-346.
@article{a13e3e1c64f8496bba1070359c54e673,
title = "Limited effect of CpG ODN in preventing type 1 diabetes in NOD mice",
abstract = "Type 1 diabetes is considered as Th1 cell mediated autoimmune disease and the suppression of Th1 cells or the activation of Th2 cells has been regarded as a plausible immunologic intervention for the prevention of type 1 diabetogenesis in a rodent model. CpG ODN is an immunostimulatory sequence primarily present in bacterial DNA, viral DNA and BCG. CpG ODN is conventionally classified as a Th1 cell activator, which has been clinically applied to cancer, allergy and infectious disease. Recently, there was a promising report of that CpG ODN administration suppressed the development of type 1 diabetes in NOD mice by inducing Th2 cell mediated cytokine. However, the antidiabetogenic effect of CpG ODN on NOD mice is controversial. Thus, two studies were serially undertaken with various kinds of CpG motif to find a more optimal sequence and administration method. In the first study, CpG ODN was vaccinated four times and pancreatic inflammation and the quantity of serum insulin subsequently evaluated. In the second study, the amounts of IFN γ and IL-4 in sera were measured as representative cytokines of Th1 and Th2 cells, respectively. As a result, vaccination or continuous injection of CpG ODN failed to show a preventive effect on type 1 diabetogenesis in NOD mice. Structural differences of CpG ODN also had no affect on the result. CpG ODN also consistently showed affect on the pancreatic pathology. The productions of IFN γ and IL-4 were detected only in the K and D type CpG ODN administration groups. Comparison of the two cytokines leads to the conclusion that CpG ODN generated a Th1-weighted response in both study groups. It was assumed that CpG ODN failed to produce Th2-weighted cytokine milieu, which can overcome the genetically determined phenotype of NOD mice. Given these results, it was concluded that the immunotherapeutic application of CpG ODN on Type 1 diabetes had clear limitations.",
author = "Lee, {Byong Jun} and Kim, {Soo Kie} and Kim, {Moon Kyu} and Park, {Eon Sub} and Cho, {Hyun Chul} and Shim, {Myung Sook} and Kim, {Mi Jin} and Shin, {Young Goo} and Chung, {Choon Hee}",
year = "2005",
month = "6",
day = "30",
doi = "10.3349/ymj.2005.46.3.341",
language = "English",
volume = "46",
pages = "341--346",
journal = "Yonsei Medical Journal",
issn = "0513-5796",
publisher = "Yonsei University College of Medicine",
number = "3",

}

Lee, BJ, Kim, SK, Kim, MK, Park, ES, Cho, HC, Shim, MS, Kim, MJ, Shin, YG & Chung, CH 2005, 'Limited effect of CpG ODN in preventing type 1 diabetes in NOD mice', Yonsei medical journal, vol. 46, no. 3, pp. 341-346. https://doi.org/10.3349/ymj.2005.46.3.341

Limited effect of CpG ODN in preventing type 1 diabetes in NOD mice. / Lee, Byong Jun; Kim, Soo Kie; Kim, Moon Kyu; Park, Eon Sub; Cho, Hyun Chul; Shim, Myung Sook; Kim, Mi Jin; Shin, Young Goo; Chung, Choon Hee.

In: Yonsei medical journal, Vol. 46, No. 3, 30.06.2005, p. 341-346.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Limited effect of CpG ODN in preventing type 1 diabetes in NOD mice

AU - Lee, Byong Jun

AU - Kim, Soo Kie

AU - Kim, Moon Kyu

AU - Park, Eon Sub

AU - Cho, Hyun Chul

AU - Shim, Myung Sook

AU - Kim, Mi Jin

AU - Shin, Young Goo

AU - Chung, Choon Hee

PY - 2005/6/30

Y1 - 2005/6/30

N2 - Type 1 diabetes is considered as Th1 cell mediated autoimmune disease and the suppression of Th1 cells or the activation of Th2 cells has been regarded as a plausible immunologic intervention for the prevention of type 1 diabetogenesis in a rodent model. CpG ODN is an immunostimulatory sequence primarily present in bacterial DNA, viral DNA and BCG. CpG ODN is conventionally classified as a Th1 cell activator, which has been clinically applied to cancer, allergy and infectious disease. Recently, there was a promising report of that CpG ODN administration suppressed the development of type 1 diabetes in NOD mice by inducing Th2 cell mediated cytokine. However, the antidiabetogenic effect of CpG ODN on NOD mice is controversial. Thus, two studies were serially undertaken with various kinds of CpG motif to find a more optimal sequence and administration method. In the first study, CpG ODN was vaccinated four times and pancreatic inflammation and the quantity of serum insulin subsequently evaluated. In the second study, the amounts of IFN γ and IL-4 in sera were measured as representative cytokines of Th1 and Th2 cells, respectively. As a result, vaccination or continuous injection of CpG ODN failed to show a preventive effect on type 1 diabetogenesis in NOD mice. Structural differences of CpG ODN also had no affect on the result. CpG ODN also consistently showed affect on the pancreatic pathology. The productions of IFN γ and IL-4 were detected only in the K and D type CpG ODN administration groups. Comparison of the two cytokines leads to the conclusion that CpG ODN generated a Th1-weighted response in both study groups. It was assumed that CpG ODN failed to produce Th2-weighted cytokine milieu, which can overcome the genetically determined phenotype of NOD mice. Given these results, it was concluded that the immunotherapeutic application of CpG ODN on Type 1 diabetes had clear limitations.

AB - Type 1 diabetes is considered as Th1 cell mediated autoimmune disease and the suppression of Th1 cells or the activation of Th2 cells has been regarded as a plausible immunologic intervention for the prevention of type 1 diabetogenesis in a rodent model. CpG ODN is an immunostimulatory sequence primarily present in bacterial DNA, viral DNA and BCG. CpG ODN is conventionally classified as a Th1 cell activator, which has been clinically applied to cancer, allergy and infectious disease. Recently, there was a promising report of that CpG ODN administration suppressed the development of type 1 diabetes in NOD mice by inducing Th2 cell mediated cytokine. However, the antidiabetogenic effect of CpG ODN on NOD mice is controversial. Thus, two studies were serially undertaken with various kinds of CpG motif to find a more optimal sequence and administration method. In the first study, CpG ODN was vaccinated four times and pancreatic inflammation and the quantity of serum insulin subsequently evaluated. In the second study, the amounts of IFN γ and IL-4 in sera were measured as representative cytokines of Th1 and Th2 cells, respectively. As a result, vaccination or continuous injection of CpG ODN failed to show a preventive effect on type 1 diabetogenesis in NOD mice. Structural differences of CpG ODN also had no affect on the result. CpG ODN also consistently showed affect on the pancreatic pathology. The productions of IFN γ and IL-4 were detected only in the K and D type CpG ODN administration groups. Comparison of the two cytokines leads to the conclusion that CpG ODN generated a Th1-weighted response in both study groups. It was assumed that CpG ODN failed to produce Th2-weighted cytokine milieu, which can overcome the genetically determined phenotype of NOD mice. Given these results, it was concluded that the immunotherapeutic application of CpG ODN on Type 1 diabetes had clear limitations.

UR - http://www.scopus.com/inward/record.url?scp=21844467475&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=21844467475&partnerID=8YFLogxK

U2 - 10.3349/ymj.2005.46.3.341

DO - 10.3349/ymj.2005.46.3.341

M3 - Article

C2 - 15988804

AN - SCOPUS:21844467475

VL - 46

SP - 341

EP - 346

JO - Yonsei Medical Journal

JF - Yonsei Medical Journal

SN - 0513-5796

IS - 3

ER -