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FoxP3+ T-Cells in Patients with B-Cell Chronic Lymphocytic Leukemia Express Cytolytic Markers and Kill Autologous B-Cells
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology.
Leiden University Medical Center.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology.
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Abstract [en]

Recent reports indicate that infiltration of FoxP3+ cells into the tumor area may be associated with better overall survival of patients with B-cell malignancies, which is in contrast to patients with non-hematopoetic tumors. Here, we demonstrate a possible mechanism to these findings. Since the tumor cell in lymphoma originates from the immune system we hypothesized that FoxP3+ T regulatory cells (Tregs) may have a suppressive role in tumor progression in patients with B-cell malignancies.

Peripheral blood was collected from 14 patients with B-cell chronic lymphocytic leukemia (B-CLL) and their Tregs were evaluated for cytolytic markers such as FasL and CD107a. We found that both conventional Tregs (CD4+ FoxP3+CD127low T-cells) and FoxP3+CD127high T-cells were significantly increased in patients with B-CLL compared to healthy controls. Further, both groups of FoxP3+ cells displayed higher expression of the degranulation marker CD107a indicating perforin/granzyme release. A flow cytometry-based cytotoxicity assay demonstrated that purified Tregs  from both patients and healthy controls could kill autologous B-cells in vitro.

In conclusion, FoxP3+ T-cells in patients with CLL show effector phenotype and may be involved in tumor cell control by their natural capacity to kill B-cells.

Keyword [en]
T regulatory cells, FoxP3, chronic lymphocytic leukemia, CD107a, effector Treg, cytotoxic Treg
Research subject
Immunology
Identifiers
URN: urn:nbn:se:uu:diva-128830OAI: oai:DiVA.org:uu-128830DiVA: diva2:331804
Available from: 2010-07-26 Created: 2010-07-26

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