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Updated: Dec 16, 2025
06:07
Measuring Mitochondrial Function of Naïve and Effector CD8 T Cells
Published on: March 28, 2025
832
TOX is expressed by exhausted and polyfunctional human effector memory CD8+ T cells
Takuya Sekine1, André Perez-Potti1, Son Nguyen2,3
1Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
Science Immunology
|July 5, 2020
Summary
Thymocyte selection-associated HMG box (TOX) is found in most human effector memory CD8+ T cells, not just exhausted ones. T-cell factor 1 (TCF-1) is more common in naive and early memory cells.
Area of Science:
- Immunology
- Molecular Biology
- T cell biology
Background:
- CD8+ T cell exhaustion is critical in cancer and chronic infections.
- TCF-1 and TOX are key transcription factors in mouse CD8+ T cell exhaustion.
- Their roles in human CD8+ T cells are not fully understood.
Purpose of the Study:
- To investigate the expression and roles of TOX and TCF-1 in human CD8+ T cell subsets.
- To determine if TOX is exclusively associated with T cell exhaustion in humans.
Main Methods:
- Mapping TOX and TCF-1 expression across human CD8+ T cell differentiation and specificity.
- Analyzing gene and protein expression signatures related to cytolytic activity.
Main Results:
- Circulating TOX+ CD8+ T cells are common in humans, found in effector memory subsets.
- TOX expression is linked to cytolytic signatures, while TCF-1 is associated with naive/early memory cells.
- Exhausted HIV-specific CD8+ T cells express TOX and less TCF-1, but polyfunctional CMV/EBV-specific and some HIV-specific T cells also express TOX.
Conclusions:
- TOX is broadly expressed in human effector memory CD8+ T cells, not solely indicative of exhaustion.
- TCF-1 expression is more characteristic of less differentiated CD8+ T cells.
- The findings refine the understanding of T cell differentiation and exhaustion markers in humans.
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