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Phenotypic and Functional Analysis of Activated Regulatory T Cells Isolated from Chronic Lymphocytic Choriomeningitis Virus-infected Mice

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-Álvarez^1,2,3, Seila Lorenzo-Herrero^1,2,3, Ana P Gonzalez-Rodriguez^2,4,3

¹Department of Functional Biology, University of Oviedo, Oviedo, Spain.

|November 11, 2017

Summary

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.

Keywords:

B cells Chronic Lymphocytic Leukemia IFN-gamma IFN-γT cells IL-2 ILT2 T cells checkpoint immunotherapy inhibitory receptors

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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.