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Diabetologia

Erschienen in:

01.07.2009 | Article

Prevention of spontaneous immune-mediated diabetes development in the LEW.1AR1-iddm rat by selective CD8⁺ T cell transfer is associated with a cytokine shift in the pancreas-draining lymph nodes

verfasst von: T. Arndt, D. Wedekind, H. Weiss, M. Tiedge, S. Lenzen, H.-J. Hedrich, A. Jörns

Erschienen in: Diabetologia | Ausgabe 7/2009

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Abstract

Aims/hypothesis

The LEW.1AR1-iddm rat is an animal model of spontaneous type 1 diabetes mellitus. This study analysed how adoptive transfer of selective T cell subpopulations affects the incidence of diabetes.

Methods

CD4⁺ or CD8⁺ T cells were isolated from diabetic LEW.1AR1-iddm rats or diabetes-resistant LEW.1AR1 rats. Cells were selectively transferred into athymic LEW.1AR1-Whn ^rnu or prediabetic LEW.1AR1-iddm rats. The animals were monitored for blood glucose, islet infiltration and immune cell composition of pancreas-draining lymph nodes.

Results

After adoptive transfer of CD4⁺ T cells from diabetic LEW.1AR1-iddm rats into athymic LEW.1AR1-Whn ^rnu rats, 50% of the recipients developed diabetes. Transfer of CD8⁺ T cells failed to induce diabetes. Only 10% of the athymic recipients became diabetic after co-transfer of CD4⁺ and CD8⁺ T cells. Adoptive transfer of CD8⁺ T cells from LEW.1AR1 or diabetic LEW.1AR1-iddm rats into prediabetic LEW.1AR1-iddm rats significantly reduced the incidence of diabetes. In protected normoglycaemic animals regulatory CD8⁺/CD25⁺ and CD4⁺/CD25⁺ T cell subpopulations that were also FOXP3-positive accumulated in the pancreas-draining lymph nodes. In this lymphatic organ, gene expression of anti-inflammatory cytokines was significantly higher than in diabetic rats.

Conclusions/interpretation

Our results show that adoptive transfer of CD4⁺ but not CD8⁺ T cells from diabetic LEW.1AR1-iddm rats induced diabetes development. Importantly, CD8⁺ T cells from diabetic LEW.1AR1-iddm rats and diabetes-resistant LEW.1AR1 rats provided protection against beta cell destruction. The accumulation of regulatory T cells in the pancreas-draining lymph nodes from protected rats indicates that transferred CD8⁺ T cells may have beneficial effects in the control of beta cell autoimmunity.

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Titel: Prevention of spontaneous immune-mediated diabetes development in the LEW.1AR1-iddm rat by selective CD8+ T cell transfer is associated with a cytokine shift in the pancreas-draining lymph nodes
verfasst von: T. Arndt
D. Wedekind
H. Weiss
M. Tiedge
S. Lenzen
H.-J. Hedrich
A. Jörns
Publikationsdatum: 01.07.2009
Verlag: Springer-Verlag
Erschienen in: Diabetologia / Ausgabe 7/2009
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-009-1348-1

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Prevention of spontaneous immune-mediated diabetes development in the LEW.1AR1-iddm rat by selective CD8⁺ T cell transfer is associated with a cytokine shift in the pancreas-draining lymph nodes

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