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Updated: Apr 30, 2026

Generation of Human Chimeric Antigen Receptor Regulatory T Cells
Published on: January 3, 2025
Tripartite motif-containing protein 30 modulates TCR-activated proliferation and effector functions in CD4+ T cells
Un Yung Choi1, Ji Yeon Hur2, Myeong Sup Lee1
1Department of Biochemistry, College of Life Science and Technology, Yonsei University, Seoul, Korea.
Abstract:
To avoid excessive activation, immune signals are tightly controlled by diverse inhibitory proteins. TRIM30, a tripartite motif (TRIM)-containing protein is one of such inhibitors known to function in macrophages. To define the roles of TRIM30, we generated Trim30 knockout (Trim30-/-) mice. Trim30 deletion caused no major developmental defects in any organs, nor showed any discernable defect in the activation of macrophages. But, Trim30-/- mice showed increased CD4/CD8 ratio when aged and Trim30-/- CD4+ T cells exhibited an abnormal response upon TCR activation, in particular in the absence of a costimulatory signal. Adoptive transfer of wild-type and Trim30-/- CD4+ T cells together into lymphopenic hosts confirmed higher proliferation of the Trim30-/- CD4+ T cells in vivo. Despite the enhanced proliferation, Trim30-/- T cells showed decreased levels of NF-κB activation and IL-2 production compared to wild-type cells. These results indicate a distinct requirement for TRIM30 in modulation of NF-κB activation and cell proliferation induced by TCR stimulation.
Insights
The study reveals that TRIM30 protein is crucial for regulating T cell responses. Its absence leads to increased T cell proliferation but decreased NF-κB activation and IL-2 production.
Area of Science:
- Immunology
- Molecular Biology
- Cellular Signaling
Background:
- Immune signal activation is tightly regulated by inhibitory proteins to prevent excessive responses.
- TRIM30 (tripartite motif-containing protein 30) is an identified inhibitor protein functioning in macrophages.
- The precise role of TRIM30 in immune regulation, particularly in T cells, requires further elucidation.
Purpose of the Study:
- To investigate the function of TRIM30 in immune regulation.
- To define the role of TRIM30 in T cell activation and proliferation.
- To understand TRIM30's impact on NF-κB signaling and cytokine production.
Main Methods:
- Generation and analysis of Trim30 knockout (Trim30-/-) mice.
- Assessment of T cell activation, proliferation, and signaling pathways (NF-κB, IL-2) upon T cell receptor (TCR) stimulation.
- Adoptive transfer experiments using wild-type and Trim30-/- CD4+ T cells in lymphopenic hosts.
Main Results:
- Trim30 deletion did not cause major developmental defects or macrophage activation issues.
- Trim30-/- mice exhibited an increased CD4/CD8 ratio with age; Trim30-/- CD4+ T cells showed enhanced proliferation in vivo, especially without costimulation.
- Despite increased proliferation, Trim30-/- T cells displayed reduced NF-κB activation and Interleukin-2 (IL-2) production.
Conclusions:
- TRIM30 plays a distinct role in modulating T cell responses, specifically impacting NF-κB activation and cell proliferation following TCR stimulation.
- The absence of TRIM30 leads to heightened T cell proliferation but impaired signaling pathways crucial for optimal T cell function.
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