McKinney and Smith provide a detailed review of the current data linking the complex metabolic profile, membrane and intracellular signaling pathways, and transcription factors together with their role in determining and modifying T cell activity and fate, particularly T cell exhaustion. They provide a clear description of the many regulators of effector and memory function needed to carefully balance an appropriate immune response.

It has become increasingly clear that changes in metabolism are not just consequences of T cell activation but instead are also essential drivers of that process that shape the extent and nature of differentiation and function. The process of T cell exhaustion has been linked to the outcome of chronic immune responses in multiple contexts, including chronic infection, cancer and autoimmunity. Factors that regulate the development and maintenance of exhaustion are of increasing interest as targets of therapeutic modulation. Studies have shown T cell immunometabolism to be integral to the control and development of T cell exhaustion. Early metabolic changes are responsible for the later emergence of exhaustion, do not simply reflect changes secondary to chronic activation and are modifiable. Increased understanding of this metabolic control promises to improve the ability to modulate T cell immunity to chronic antigen stimulation in multiple contexts.

Author Info: (1) Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Cambridge, UK. efm30@medschl.cam.ac.uk. (2) Department of Medicine, University of Cambridge School

Author Info: (1) Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Cambridge, UK. efm30@medschl.cam.ac.uk. (2) Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Cambridge, UK.

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