FoxP3+ T-Cells in Patients with B-Cell Chronic Lymphocytic Leukemia Express Cytolytic Markers and Kill Autologous B-Cells
(English)Manuscript (preprint) (Other academic)
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.
T regulatory cells, FoxP3, chronic lymphocytic leukemia, CD107a, effector Treg, cytotoxic Treg
Research subject Immunology
IdentifiersURN: urn:nbn:se:uu:diva-128830OAI: oai:DiVA.org:uu-128830DiVA: diva2:331804