Adoptive Transfer of Autoimmune Diabetes Mellitus to Athymic Rats: Synergy of CD4+ and CD8+ T Cells and Prevention by RT6+ T Cells

Whalen, Barbara J.; Greiner, Dale L.; Mordes, John P.; Rossini, Aldo A.

doi:10.1006/jaut.1994.1065

Cited by 46 publications

(30 citation statements)

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“…Thus, a clear autoaggressive potential of CD4 + T cells was seen, in line with several studies on BB-DP rats and NOD mice [7][8][9][10][11][12]. The predominant role of CD4 + T cells has been previously demonstrated by selective transfer of CD4 + or CD8 + T cells in immunodeficient NOD strains, whereas CD8 + T cell subsets were not diabetogenic [7,16].…”

Section: Discussionsupporting

confidence: 85%

“…The only difference between the LEW.1AR1-iddm rat and the background strain is a mutation on chromosome 1 within Iddm8 (RNO1q43-51) [4,5]. Adoptive transfer of T cells from diabetic LEW.1AR1-iddm rats to prediabetic LEW.1AR1-iddm rats significantly increased the incidence of diabetes [6] in agreement with studies on NOD mice and BB-DP rats [7][8][9][10][11][12]. The autoreactive potential can be transferred through immune cells from diabetic LEW.1AR1-iddm rats into athymic nude LEW.1AR1-Whn rnu animals, but not to the diabetes-resistant LEW.1AR1 background strain [6].…”

Section: Introductionsupporting

confidence: 80%

“…The predominant role of CD4 + T cells has been previously demonstrated by selective transfer of CD4 + or CD8 + T cells in immunodeficient NOD strains, whereas CD8 + T cell subsets were not diabetogenic [7,16]. On the other hand, CD8 + T cells are required for adoptive transfer of the diabetic syndrome in BB-DP rats [11,17]. The apparent discrepancy between these studies and the LEW.1AR1-iddm rat may be at least in part explained by the lymphopenic background of the BB rat, which could potentially affect the balance between autoaggressive and Treg subtypes.…”

Section: Discussionmentioning

confidence: 82%

“…The cell suspensions were cultured with 10 µg/ml concanavalin A (Biochrom, Berlin, Germany) for 72 h after isolation of specific T cell subpopulations as described before [6] to obtain a sufficient number of T cells for transfer to non-irradiated animals. We used concanavalin A stimulation in accordance with adoptive transfer protocols in the BB rat [11] because until now it has not been possible to identify T cell activating islet autoantigens in this model. The purity of each T cell population was determined by flow cytometry before and after stimulation with concanavalin A and was consistently >98%.…”

Section: Methodsmentioning

confidence: 99%

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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

et al. 2009

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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 cotransfer 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. Keywords

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Section: Discussionsupporting

confidence: 85%

Section: Introductionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 82%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

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

et al. 2009

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“…CD4 + T cells are required for the initiation and promotion of diabetes development in the BBdp rat [50]. CD8 + T cells are also required as effectors, but are almost absent in BBdp rats [51], and showed little response to wheat protein antigens in the present study (Fig.…”

Section: Discussionmentioning

confidence: 47%

Wheat protein-induced proinflammatory T helper 1 bias in mesenteric lymph nodes of young diabetes-prone rats

Chakir¹,

Lefebvre

Wang³

et al. 2005

Diabetologia

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Aims/hypothesis: Type 1 diabetes is the result of an inflammatory T helper 1 (Th1) lymphocyte-mediated beta cell destructive process. The majority of diabetesprone BioBreeding (BBdp) rats fed wheat protein-based diets, such as NTP-2000, develop type 1 diabetes and display a mild coeliac-like enteropathy. Mesenteric lymph nodes (MLNs), which drain the gut, are the major inductive site where dietary antigens are recognised in the gut-associated lymphoid tissue (GALT). We hypothesised that this compartment could be a site of abnormal wheat proteininduced Th1 cell activation. Methods: MLN cells were isolated from BBdp and BB control (BBc) rats that were fed NTP-2000 or a hydrolysed casein (HC)-based diet at ages that pre-date classic insulitis. The inflammatory status, phenotype and proliferation of these cells in response to wheat protein were determined. Results: The expression ratio of T-bet : Gata3, master transcription factors for Th1 and Th2 cytokines, was increased in the MLN from NTP-2000-fed BBdp rats compared with that from BBc rats, mainly due to decreased Gata3 expression. CD3 + CD4 + IFN-γ + T cells were more prevalent in the MLN of wheatfed BBdp rats, but remained at control levels in BBdp rats fed a diabetes-retardant HC diet. BBdp MLN cells proliferated in response to wheat protein antigens in a specific, dose-dependent manner, and >93% of cells were CD3 + CD4 + T cells. This proliferation was associated with a low proportion of CD4 + CD25 + T cells and a high proportion of dendritic cells in the MLN of BBdp rats. Conclusions/ interpretation: Before insulitis is established, the MLNs of wheat-fed BBdp rats contain an unusually high proportion of Th1 cells that proliferate specifically in response to wheat protein antigens.

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The BB/Wor Rat and the Balance Hypothesis of Autoimmunity

Mordes

Bortell

Doukas

et al. 1996

Diabetes Metab. Rev.

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Adoptive Transfer of Autoimmune Diabetes Mellitus to Athymic Rats: Synergy of CD4+ and CD8+ T Cells and Prevention by RT6+ T Cells

Cited by 46 publications

References 0 publications

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

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

Wheat protein-induced proinflammatory T helper 1 bias in mesenteric lymph nodes of young diabetes-prone rats

The BB/Wor Rat and the Balance Hypothesis of Autoimmunity

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