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Updated: Mar 2, 2026
Phenotypic and Functional Analysis of Activated Regulatory T Cells Isolated from Chronic Lymphocytic Choriomeningitis Virus-infected Mice
Published on: June 22, 2016
The microRNA miR-31 inhibits CD8+ T cell function in chronic viral infection
Howell F Moffett1, Adam N R Cartwright1, Hye-Jung Kim1
1Department of Cancer Immunology &Virology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Abstract:
During infection, antigen-specific T cells undergo tightly regulated developmental transitions controlled by transcriptional and post-transcriptional regulation of gene expression. We found that the microRNA miR-31 was strongly induced by activation of the T cell antigen receptor (TCR) in a pathway involving calcium and activation of the transcription factor NFAT. During chronic infection with lymphocytic choriomeningitis virus (LCMV) clone 13, miR-31-deficent mice recovered from clinical disease, while wild-type mice continued to show signs of disease. This disease phenotype was explained by the presence of larger numbers of cytokine-secreting LCMV-specific CD8+ T cells in miR-31-deficent mice than in wild-type mice. Mechanistically, miR-31 increased the sensitivity of T cells to type I interferons, which interfered with effector T cell function and increased the expression of several proteins related to T cell dysfunction during chronic infection. These studies identify miR-31 as an important regulator of T cell exhaustion in chronic infection.
Insights
MicroRNA miR-31 regulates T cell exhaustion during chronic infection. Mice lacking miR-31 showed improved recovery from disease by maintaining functional CD8+ T cells.
Area of Science:
- Immunology
- Molecular Biology
- Virology
Background:
- T cell activation involves complex gene regulation.
- Chronic infections can lead to T cell exhaustion, impairing immune responses.
Purpose of the Study:
- To investigate the role of microRNA miR-31 in T cell regulation during infection.
- To understand miR-31's impact on T cell exhaustion in chronic viral infections.
Main Methods:
- Studied miR-31 induction via T cell receptor (TCR) signaling.
- Utilized a lymphocytic choriomeningitis virus (LCMV) mouse model for chronic infection.
- Compared disease progression and T cell function in miR-31-deficient and wild-type mice.
Main Results:
- miR-31 was induced by T cell receptor (TCR) activation through calcium and NFAT.
- miR-31-deficient mice exhibited reduced disease severity during chronic LCMV infection.
- Absence of miR-31 led to increased numbers of functional, cytokine-secreting CD8+ T cells.
- miR-31 enhanced T cell sensitivity to type I interferons, promoting dysfunction.
Conclusions:
- miR-31 is a key regulator of T cell exhaustion during chronic viral infections.
- Targeting miR-31 may offer therapeutic strategies to restore T cell function in chronic diseases.
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