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Oral Sessions| November 16, 2005

Mucosal Foxp3⁺ Regulatory T Cells Show Significant Numerical Differences in Patients with Intestinal Graft-Versus-Host Disease Compared to Infectious Diseases of the Gut.

Kathrin Rieger,

Kathrin Rieger *

¹ Charite University Medicine Berlin, Campus Benjamin-Franklin, Medical Clinic III, Hematology, Oncology and Transfusion Medicine, Berlin, Germany; ² Charite University Medicine Berlin, Campus Benjamin-Franklin, Consultation and Reference Center for Lymph Node Pathology and Haemapathology-Institute for Pathology, Berlin, Germany; ³ Charite University Medicine Berlin, Campus Benjamin-Franklin, Gastroenterology Medical Clinic II, Berlin, Germany; ⁴ University of Rostock, Division of Hematology and Oncology, Rostock, Germany; ⁵ University of Rostock, Department of Pathology, Rostock, Germany; ⁶ University School of Medicine Dresden, Department of Gastroenterology, Dresden, Germany and ⁷ University School of Medicine Dresden, Department of Hematology, Dresden, Germany .

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Christoph Loddenkemper,

Christoph Loddenkemper *

¹ Charite University Medicine Berlin, Campus Benjamin-Franklin, Medical Clinic III, Hematology, Oncology and Transfusion Medicine, Berlin, Germany; ² Charite University Medicine Berlin, Campus Benjamin-Franklin, Consultation and Reference Center for Lymph Node Pathology and Haemapathology-Institute for Pathology, Berlin, Germany; ³ Charite University Medicine Berlin, Campus Benjamin-Franklin, Gastroenterology Medical Clinic II, Berlin, Germany; ⁴ University of Rostock, Division of Hematology and Oncology, Rostock, Germany; ⁵ University of Rostock, Department of Pathology, Rostock, Germany; ⁶ University School of Medicine Dresden, Department of Gastroenterology, Dresden, Germany and ⁷ University School of Medicine Dresden, Department of Hematology, Dresden, Germany .

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Jochen Maul,

Jochen Maul *

¹ Charite University Medicine Berlin, Campus Benjamin-Franklin, Medical Clinic III, Hematology, Oncology and Transfusion Medicine, Berlin, Germany; ² Charite University Medicine Berlin, Campus Benjamin-Franklin, Consultation and Reference Center for Lymph Node Pathology and Haemapathology-Institute for Pathology, Berlin, Germany; ³ Charite University Medicine Berlin, Campus Benjamin-Franklin, Gastroenterology Medical Clinic II, Berlin, Germany; ⁴ University of Rostock, Division of Hematology and Oncology, Rostock, Germany; ⁵ University of Rostock, Department of Pathology, Rostock, Germany; ⁶ University School of Medicine Dresden, Department of Gastroenterology, Dresden, Germany and ⁷ University School of Medicine Dresden, Department of Hematology, Dresden, Germany .

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Thomas Fietz,

Thomas Fietz *

¹ Charite University Medicine Berlin, Campus Benjamin-Franklin, Medical Clinic III, Hematology, Oncology and Transfusion Medicine, Berlin, Germany; ² Charite University Medicine Berlin, Campus Benjamin-Franklin, Consultation and Reference Center for Lymph Node Pathology and Haemapathology-Institute for Pathology, Berlin, Germany; ³ Charite University Medicine Berlin, Campus Benjamin-Franklin, Gastroenterology Medical Clinic II, Berlin, Germany; ⁴ University of Rostock, Division of Hematology and Oncology, Rostock, Germany; ⁵ University of Rostock, Department of Pathology, Rostock, Germany; ⁶ University School of Medicine Dresden, Department of Gastroenterology, Dresden, Germany and ⁷ University School of Medicine Dresden, Department of Hematology, Dresden, Germany .

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Daniel Wolff,

Daniel Wolff *

¹ Charite University Medicine Berlin, Campus Benjamin-Franklin, Medical Clinic III, Hematology, Oncology and Transfusion Medicine, Berlin, Germany; ² Charite University Medicine Berlin, Campus Benjamin-Franklin, Consultation and Reference Center for Lymph Node Pathology and Haemapathology-Institute for Pathology, Berlin, Germany; ³ Charite University Medicine Berlin, Campus Benjamin-Franklin, Gastroenterology Medical Clinic II, Berlin, Germany; ⁴ University of Rostock, Division of Hematology and Oncology, Rostock, Germany; ⁵ University of Rostock, Department of Pathology, Rostock, Germany; ⁶ University School of Medicine Dresden, Department of Gastroenterology, Dresden, Germany and ⁷ University School of Medicine Dresden, Department of Hematology, Dresden, Germany .

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Harald Terpe,

Harald Terpe *

¹ Charite University Medicine Berlin, Campus Benjamin-Franklin, Medical Clinic III, Hematology, Oncology and Transfusion Medicine, Berlin, Germany; ² Charite University Medicine Berlin, Campus Benjamin-Franklin, Consultation and Reference Center for Lymph Node Pathology and Haemapathology-Institute for Pathology, Berlin, Germany; ³ Charite University Medicine Berlin, Campus Benjamin-Franklin, Gastroenterology Medical Clinic II, Berlin, Germany; ⁴ University of Rostock, Division of Hematology and Oncology, Rostock, Germany; ⁵ University of Rostock, Department of Pathology, Rostock, Germany; ⁶ University School of Medicine Dresden, Department of Gastroenterology, Dresden, Germany and ⁷ University School of Medicine Dresden, Department of Hematology, Dresden, Germany .

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Beate Steiner,

Beate Steiner *

¹ Charite University Medicine Berlin, Campus Benjamin-Franklin, Medical Clinic III, Hematology, Oncology and Transfusion Medicine, Berlin, Germany; ² Charite University Medicine Berlin, Campus Benjamin-Franklin, Consultation and Reference Center for Lymph Node Pathology and Haemapathology-Institute for Pathology, Berlin, Germany; ³ Charite University Medicine Berlin, Campus Benjamin-Franklin, Gastroenterology Medical Clinic II, Berlin, Germany; ⁴ University of Rostock, Division of Hematology and Oncology, Rostock, Germany; ⁵ University of Rostock, Department of Pathology, Rostock, Germany; ⁶ University School of Medicine Dresden, Department of Gastroenterology, Dresden, Germany and ⁷ University School of Medicine Dresden, Department of Hematology, Dresden, Germany .

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Erika Berg,

Erika Berg *

¹ Charite University Medicine Berlin, Campus Benjamin-Franklin, Medical Clinic III, Hematology, Oncology and Transfusion Medicine, Berlin, Germany; ² Charite University Medicine Berlin, Campus Benjamin-Franklin, Consultation and Reference Center for Lymph Node Pathology and Haemapathology-Institute for Pathology, Berlin, Germany; ³ Charite University Medicine Berlin, Campus Benjamin-Franklin, Gastroenterology Medical Clinic II, Berlin, Germany; ⁴ University of Rostock, Division of Hematology and Oncology, Rostock, Germany; ⁵ University of Rostock, Department of Pathology, Rostock, Germany; ⁶ University School of Medicine Dresden, Department of Gastroenterology, Dresden, Germany and ⁷ University School of Medicine Dresden, Department of Hematology, Dresden, Germany .

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Stefan Miehlke,

Stefan Miehlke *

¹ Charite University Medicine Berlin, Campus Benjamin-Franklin, Medical Clinic III, Hematology, Oncology and Transfusion Medicine, Berlin, Germany; ² Charite University Medicine Berlin, Campus Benjamin-Franklin, Consultation and Reference Center for Lymph Node Pathology and Haemapathology-Institute for Pathology, Berlin, Germany; ³ Charite University Medicine Berlin, Campus Benjamin-Franklin, Gastroenterology Medical Clinic II, Berlin, Germany; ⁴ University of Rostock, Division of Hematology and Oncology, Rostock, Germany; ⁵ University of Rostock, Department of Pathology, Rostock, Germany; ⁶ University School of Medicine Dresden, Department of Gastroenterology, Dresden, Germany and ⁷ University School of Medicine Dresden, Department of Hematology, Dresden, Germany .

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Martin Bornhaeuser,

Martin Bornhaeuser *

¹ Charite University Medicine Berlin, Campus Benjamin-Franklin, Medical Clinic III, Hematology, Oncology and Transfusion Medicine, Berlin, Germany; ² Charite University Medicine Berlin, Campus Benjamin-Franklin, Consultation and Reference Center for Lymph Node Pathology and Haemapathology-Institute for Pathology, Berlin, Germany; ³ Charite University Medicine Berlin, Campus Benjamin-Franklin, Gastroenterology Medical Clinic II, Berlin, Germany; ⁴ University of Rostock, Division of Hematology and Oncology, Rostock, Germany; ⁵ University of Rostock, Department of Pathology, Rostock, Germany; ⁶ University School of Medicine Dresden, Department of Gastroenterology, Dresden, Germany and ⁷ University School of Medicine Dresden, Department of Hematology, Dresden, Germany .

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Thomas Schneider,

Thomas Schneider *

¹ Charite University Medicine Berlin, Campus Benjamin-Franklin, Medical Clinic III, Hematology, Oncology and Transfusion Medicine, Berlin, Germany; ² Charite University Medicine Berlin, Campus Benjamin-Franklin, Consultation and Reference Center for Lymph Node Pathology and Haemapathology-Institute for Pathology, Berlin, Germany; ³ Charite University Medicine Berlin, Campus Benjamin-Franklin, Gastroenterology Medical Clinic II, Berlin, Germany; ⁴ University of Rostock, Division of Hematology and Oncology, Rostock, Germany; ⁵ University of Rostock, Department of Pathology, Rostock, Germany; ⁶ University School of Medicine Dresden, Department of Gastroenterology, Dresden, Germany and ⁷ University School of Medicine Dresden, Department of Hematology, Dresden, Germany .

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Martin Zeitz,

Martin Zeitz *

¹ Charite University Medicine Berlin, Campus Benjamin-Franklin, Medical Clinic III, Hematology, Oncology and Transfusion Medicine, Berlin, Germany; ² Charite University Medicine Berlin, Campus Benjamin-Franklin, Consultation and Reference Center for Lymph Node Pathology and Haemapathology-Institute for Pathology, Berlin, Germany; ³ Charite University Medicine Berlin, Campus Benjamin-Franklin, Gastroenterology Medical Clinic II, Berlin, Germany; ⁴ University of Rostock, Division of Hematology and Oncology, Rostock, Germany; ⁵ University of Rostock, Department of Pathology, Rostock, Germany; ⁶ University School of Medicine Dresden, Department of Gastroenterology, Dresden, Germany and ⁷ University School of Medicine Dresden, Department of Hematology, Dresden, Germany .

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Harald Stein,

Harald Stein *

¹ Charite University Medicine Berlin, Campus Benjamin-Franklin, Medical Clinic III, Hematology, Oncology and Transfusion Medicine, Berlin, Germany; ² Charite University Medicine Berlin, Campus Benjamin-Franklin, Consultation and Reference Center for Lymph Node Pathology and Haemapathology-Institute for Pathology, Berlin, Germany; ³ Charite University Medicine Berlin, Campus Benjamin-Franklin, Gastroenterology Medical Clinic II, Berlin, Germany; ⁴ University of Rostock, Division of Hematology and Oncology, Rostock, Germany; ⁵ University of Rostock, Department of Pathology, Rostock, Germany; ⁶ University School of Medicine Dresden, Department of Gastroenterology, Dresden, Germany and ⁷ University School of Medicine Dresden, Department of Hematology, Dresden, Germany .

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Eckhard Thiel,

Eckhard Thiel

¹ Charite University Medicine Berlin, Campus Benjamin-Franklin, Medical Clinic III, Hematology, Oncology and Transfusion Medicine, Berlin, Germany; ² Charite University Medicine Berlin, Campus Benjamin-Franklin, Consultation and Reference Center for Lymph Node Pathology and Haemapathology-Institute for Pathology, Berlin, Germany; ³ Charite University Medicine Berlin, Campus Benjamin-Franklin, Gastroenterology Medical Clinic II, Berlin, Germany; ⁴ University of Rostock, Division of Hematology and Oncology, Rostock, Germany; ⁵ University of Rostock, Department of Pathology, Rostock, Germany; ⁶ University School of Medicine Dresden, Department of Gastroenterology, Dresden, Germany and ⁷ University School of Medicine Dresden, Department of Hematology, Dresden, Germany .

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Lutz Uharek

Lutz Uharek *

¹ Charite University Medicine Berlin, Campus Benjamin-Franklin, Medical Clinic III, Hematology, Oncology and Transfusion Medicine, Berlin, Germany; ² Charite University Medicine Berlin, Campus Benjamin-Franklin, Consultation and Reference Center for Lymph Node Pathology and Haemapathology-Institute for Pathology, Berlin, Germany; ³ Charite University Medicine Berlin, Campus Benjamin-Franklin, Gastroenterology Medical Clinic II, Berlin, Germany; ⁴ University of Rostock, Division of Hematology and Oncology, Rostock, Germany; ⁵ University of Rostock, Department of Pathology, Rostock, Germany; ⁶ University School of Medicine Dresden, Department of Gastroenterology, Dresden, Germany and ⁷ University School of Medicine Dresden, Department of Hematology, Dresden, Germany .

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Blood (2005) 106 (11): 596.

https://doi.org/10.1182/blood.V106.11.596.596

Abstract

Objectives: The clinical diagnosis of intestinal GvHD is often complicated, even if bioptical material is present. So far, it is difficult to separate between GvHD and infectious complications, since distinguishing immunological features are not established. In a multicenter study, we quantified Foxp3⁺ immunoregulatory T cells (T_reg) and effector T cells in the intestinal mucosa of patients with acute or chronic GvHD, and infectious diseases of the gut.

Methods: 95 paraffin-embedded tissue samples (44 with acute GvHD, 18 with chronic GvHD and 33 without histological GvHD) derived from intestinal biopsies from 49 patients undergoing allogeneic stem cell transplantation, and 12 inflammatory controls (6 patients with CMV-colitis and 6 with diverticulitis) were analysed by double immunoenzymatic labeling. Serial sections were stained for CD4, CD8 and co-stained for CD3/Foxp3 and CD25/Foxp3. In addition, lamina propria lymphocytes were isolated from intestinal biopsies by collagenase digestion and further characterized by flow-cytometry in comparison to peripheral blood lymphocytes in 24 patients with suspected GvHD after allogeneic stem cell transplantation and healthy controls.

Results: The number of CD3⁺ T cells was extensively increased in intestinal GvHD, CMV colitis and diverticulitis. Though the number of CD8⁺ cells was similar, we saw striking differences in the frequency of Foxp3⁺ T_reg in relation to CD8⁺ effector T cells. The number of Foxp3⁺ T cells per 100 CD8⁺ T cells was significantly lower in GvHD samples (1.7 ± 0.2) than in CMV colitis (27.4 ± 2.5) or diverticulitis (50.0 ± 4.4). Within the allogeneic transplanted patients, samples without histological signs of GvHD had also significantly elevated numbers of Foxp3⁺/100 CD8⁺ T cells (14.1 ± 2.0) compared to acute (1.7 ± 0.2) and chronic GvHD (2.9 ± 0.8) and healthy controls (2.0 ± 0.3).

Conclusion: In contrast to infectious diseases of the gut, GvHD is characterized by a considerable decrease of mucosal T^reg cells. Together with recent experimental data, our results give new insights in the pathophysiology of intestinal GvHD and can be helpful for the precise diagnosis of intestinal complications after allogeneic stem cell transplantation.

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Corresponding author

2005, The American Society of Hematology

2005

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