T effector (T
eff) cells are the workhorse of the immune system, the Navy Seals amongst the lymphocytes, and the S.W.A.T. team for pathogen defense. They come in quick, they come in hot, and they usually do not take prisoners. They are absolute beasts when it comes to rapidly responding to and fighting viral and bacterial infections as well as cancer. But ask them to trench in for the long haul, and they may suffer from fatigue and debilitation, a syndrome known as T cell exhaustion.
The Burnout Syndrome of the Immune System: T Cell Exhaustion
T cell exhaustion is a state of dysfunction in mostly CD8+ T
eff cells occurring with prolonged, persistent antigenic stimulation in chronic infections or cancer. It is characterized by the gradual and progressive loss of effector function, and can result in the total inability to counteract an immunogenic threat. It may culminate in the physical loss of the responding T cell population. T cell exhaustion is predominantly prolonged antigenic stimulation, often combined with increased exposure to inhibitory receptor ligands binding and activating their receptors such as PD-1, LAG-3, CTLA-4, or TIM-3. The exhaustive nature of this lasting stimulation in combination with inhibitory repression is often compounded by a diminishing help from CD4+ T
helper cells and exposure to inhibitory cytokines from other leukocyte sources.
T cell exhaustion plays a significant role in the failure to combat chronic infections (e.g., hepatitis B or C, or HIV), and is a leading factor permitting tumor outgrowth. Preventing and combatting T cell exhaustion is a core focus in immunology, and promising advances have been made with antibodies blocking inhibitory receptors or ligands. T cell exhaustion is also critical in the CAR-T cell field, as it poses severe barriers for successful CAR-T cell therapy.
- Infographic showing the phenotype of and main factors contributing to T cell exhaustion.
- T cell exhaustion is the functional depletion of effector T cells due to extended stimuli.
- T cell exhaustion is a major concern in chronic inflammation and tumor immune response.
