Regulatory CD4+CD25+ cells reverse imbalances in the T cell pool of bone marrow transplanted TG 26 mice leading to the prevention of colitis

Veltkamp, Claudia; Sartor, R. Balfour; Giese, Thomas; Autschbach, Frank; Kaden, Ines; Veltkamp, Roland; Rost, D; Kallinowski, B.; Stremmel, Wolfgang

doi:10.1136/gut.2004.046953

Cited by 11 publications

(17 citation statements)

References 42 publications

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“…Our methods do not allow us to determine whether these cells developed de novo in the thymus or represent CD4 + CD25 + T cells that had immigrated into the thymus after transfer. In any case, the increase in Treg cells in the thymus of BM + CD25 + CD4 + →Tgε26 mice in the present experiments together with the previously reported decrease of Treg cells in MLN of BM→Tgε26 mice [11] and the protective effect of Treg cells against colitis [11] suggest a defect in positive selection of Treg cells in the abnormal thymus of Tgε26 mice as a central factor in the pathogenesis of colitis in this model.…”

Section: Discussionsupporting

confidence: 82%

“…In previous experiments, CD4 + CD25 + Treg cell transfer normalized the number of peripheral T lymphocytes thereby preventing colitis in BM‐transplanted Tgε26 mice [11]. This result prompted us to investigate whether Treg cells act only in the periphery or whether T‐cell subgroup normalization is already induced in the thymus.…”

Section: Resultsmentioning

confidence: 98%

“…A diminished number of regulatory CD4 + CD25 + cells has been demonstrated in the spleen and in the mesenteric lymph nodes (MLN) of BM‐transplanted Tgε26 mice [11, 26]. We have shown previously that transfer of regulatory CD4 + CD25 + cells together with BM normalizes the peripheral T‐cell pool and function and prevents colitis [11]. While the peripheral mechanisms of action of regulatory CD4 + CD25 + cells in this model and in the CD4 + CD45Rb transfer SCID colitis mouse model [reviewed in 27] have been studied, the effect of CD4 + CD25 + cells on the thymus of Tgε26 mice transplanted bone marrow from syngenic WT mice (BM→Tgε26) is unknown.…”

Section: Introductionmentioning

confidence: 99%

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Regulatory CD4⁺CD25⁺ T Cells Prevent Thymic Dysfunction in Experimental Chronic Colitis

Veltkamp¹,

Ruhwald²,

Veltkamp³

et al. 2007

Scand J Immunol

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Chronic colitis in T‐cell deficient Tgε26 mice develops due to a dysfunction of the thymus which generates colitogenic T cells after bone marrow (BM) transplantation. Regulatory CD4+CD25+ T cells have been shown to prevent colitis in this model by normalizing the peripheral T‐cell pool. We tested the hypothesis that T‐cell normalization takes place in the thymus. Tgε26 mice were transplanted with BM (BM→Tgε26 mice) and consequently received either CD4+CD25+ or CD4+CD25− cells from syngenic wild type mice. Furthermore, untransplanted Tgε26 mice received CD4+CD25+ or CD4+CD25− cells or complete mesenteric lymph node cells. Transfer of regulatory. CD4+CD25+ cells normalized the total number of thymocytes and the percentage and number of double positive CD4+CD8+ cells in transplanted mice while percentage of single positive CD4+ and CD8+ thymocytes in BM→Tgε26 mice was reduced upon CD4+CD25+ transfer. Timing of CD4+CD25+ cell injection was important as transfer later than 7 days after BM transplantation failed to prevent abnormal thymic T‐cell distribution in BM→Tgε26 mice. Isolated CD4+CD25+ cell transfer without preceding BM transplantation failed to reconstitute thymic architecture. Differences of thymic cell composition could not be exclusively explained by presence or absence of colitis, respectively, because 19 days after BM transplantation when both groups showed no histological signs of colitis, animals transferred with CD4+CD25+ T cells had a significantly higher percentage and number of CD4+CD25+ thymocytes and CD4+Foxp3+ cells than BM→Tgε26 mice. In conclusion, early CD4+CD25+ cotransfer prevents thymic dysfunction which underlies immune‐mediated bowel inflammation in BM→Tgε26 mice.

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Section: Discussionsupporting

confidence: 82%

Section: Resultsmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

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Regulatory CD4⁺CD25⁺ T Cells Prevent Thymic Dysfunction in Experimental Chronic Colitis

Veltkamp¹,

Ruhwald²,

Veltkamp³

et al. 2007

Scand J Immunol

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“…Although bone marrow repopulation can restore most thymic functions, those mice still suffer from a numeric defect of Treg cells, resulting in chronic colitis. Interestingly, the onset of colitis in this model is accompanied by a diminished thymic cellularity, whereas treatment with anti-TNFα or Treg cells prevents thymic collapse and leads to development of functional Treg cells 38 39. These results implicate a colitis-induced feedback mechanism leading to a defective thymic production of Treg cells in genetically susceptible hosts.…”

Section: Discussionmentioning

confidence: 73%

Apoptosis of regulatory T lymphocytes is increased in chronic inflammatory bowel disease and reversed by anti-TNF treatment

Veltkamp

Anstaett

Wahl

et al. 2011

Gut

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“…Administration of regulatory T cells in mice with established colitis can cure the disease via pathways involving both IL-10/TGF-b-dependent and independent mechanisms [10,11]. Colitis occurs in mice in which regulatory T cells fail to develop properly [12,13].…”

Section: Introductionmentioning

confidence: 98%

Diminution of Circulating CD4+CD25high T Cells in Naïve Crohn’s Disease

et al. 2008

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Crohn's disease is considered to be caused either by an excess of T-cell effector functions and/or by a defective regulatory T-cell compartment. The aim of this study was to assess in Crohn's disease the frequency of circulating CD4(+)CD25(high) T cells that possess regulatory T-cell functions and CD4(+)CD25(low) T cells that contain activated T cells. Flow cytometry of peripheral blood was used to assess CD4(+)CD25(high) and CD4(+)CD25(low) T-cell frequencies in a cohort of 66 patients with Crohn's disease in comparison to 19 patients with ulcerative colitis and 31 healthy individuals enrolled as controls. The CD4(+)CD25(high) T-cell frequency was significantly lowered in naïve Crohn's disease (P = 0.013) and in ulcerative colitis (P = 0.001). CD4(+)CD25(low) T-cell frequency was increased in Crohn's disease (P = 0.0001) and in ulcerative colitis (P = 0.0002). Both CD4(+)CD25(high) and CD4(+)CD25(low) T-cell frequencies are altered in naïve Crohn's disease resulting in an imbalance between both populations and a relative contraction of the CD4(+)CD25(high) T-cell population.

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Regulatory CD4+CD25+ cells reverse imbalances in the T cell pool of bone marrow transplanted TG 26 mice leading to the prevention of colitis

Cited by 11 publications

References 42 publications

Regulatory CD4⁺CD25⁺ T Cells Prevent Thymic Dysfunction in Experimental Chronic Colitis

Regulatory CD4⁺CD25⁺ T Cells Prevent Thymic Dysfunction in Experimental Chronic Colitis

Apoptosis of regulatory T lymphocytes is increased in chronic inflammatory bowel disease and reversed by anti-TNF treatment

Diminution of Circulating CD4+CD25high T Cells in Naïve Crohn’s Disease

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Regulatory CD4+CD25+ cells reverse imbalances in the T cell pool of bone marrow transplanted TG 26 mice leading to the prevention of colitis

Cited by 11 publications

References 42 publications

Regulatory CD4+CD25+ T Cells Prevent Thymic Dysfunction in Experimental Chronic Colitis

Regulatory CD4+CD25+ T Cells Prevent Thymic Dysfunction in Experimental Chronic Colitis

Apoptosis of regulatory T lymphocytes is increased in chronic inflammatory bowel disease and reversed by anti-TNF treatment

Diminution of Circulating CD4+CD25high T Cells in Naïve Crohn’s Disease

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Product

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Regulatory CD4⁺CD25⁺ T Cells Prevent Thymic Dysfunction in Experimental Chronic Colitis

Regulatory CD4⁺CD25⁺ T Cells Prevent Thymic Dysfunction in Experimental Chronic Colitis