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Phenotypic and Functional Analysis of Activated Regulatory T Cells Isolated from Chronic Lymphocytic Choriomeningitis Virus-infected Mice
Published on: June 22, 2016
Ig-like transcript 2 (ILT2) suppresses T cell function in chronic lymphocytic leukemia
Mónica Villa-Álvarez1,2,3, Seila Lorenzo-Herrero1,2,3, Ana P Gonzalez-Rodriguez2,4,3
1Department of Functional Biology, University of Oviedo, Oviedo, Spain.
Abstract:
Chronic lymphocytic leukemia (CLL) is associated with a profound dysregulation of the immune system. Loss of T cell function is frequently caused in cancer by sustained signaling of inhibitory receptors. Here, we analyzed the role of the novel inhibitory receptor Ig-like transcript 2 (ILT2) in the pathogenesis of CLL. We observed that ILT2 expression was markedly reduced on leukemic cells, whereas it was increased on CD8 and CD4 T cells from CLL patients, particularly in those patients harboring chromosome 11q deletion, which includes the ATM gene. A deep dysregulation of ILT2 ligands expression in leukemia cells was also observed. ILT2 impaired the activation and proliferation of CD4 and CD8 T cells in CLL patients, but it had no effect in leukemic cells. ILT2 downregulated the production of IL-2 by CD4 T cells of CLL patients and induced the expression of cytokines that promote the survival of leukemic cells, such as IFN-γ, by T cells. Importantly, ILT2 blockade restored the activation, proliferation and cytokine production of T cells. In conclusion, we describe a novel immune inhibitory pathway that is upregulated in CLL and delineate a new potential target to be explored in this disease.
Insights
In chronic lymphocytic leukemia (CLL), the inhibitory receptor ILT2 is increased on T cells, impairing their function. Blocking ILT2 restores T cell activity, suggesting it as a potential therapeutic target for CLL.
Area of Science:
- Immunology
- Hematology
- Cancer Biology
Background:
- Chronic lymphocytic leukemia (CLL) involves significant immune system dysregulation.
- Impaired T cell function in cancer is often linked to inhibitory receptor signaling.
Purpose of the Study:
- To investigate the role of the novel inhibitory receptor Ig-like transcript 2 (ILT2) in CLL pathogenesis.
- To understand ILT2's impact on T cell function and leukemic cell survival in CLL.
Main Methods:
- Analysis of ILT2 expression on T cells and leukemic cells from CLL patients.
- Assessment of ILT2's effect on T cell activation, proliferation, and cytokine production.
- Evaluation of ILT2 blockade efficacy in restoring T cell function.
Main Results:
- ILT2 expression was reduced on CLL cells but increased on CD4+ and CD8+ T cells, especially in patients with 11q deletion.
- ILT2 impaired T cell activation and proliferation while downregulating IL-2 production.
- ILT2 induced T cell expression of IFN-γ, promoting leukemic cell survival.
- ILT2 blockade successfully restored T cell activation, proliferation, and cytokine production.
Conclusions:
- A novel immune inhibitory pathway involving ILT2 is upregulated in CLL.
- ILT2 plays a critical role in T cell dysfunction and leukemic cell survival in CLL.
- ILT2 blockade represents a potential therapeutic strategy for CLL.
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