Typical occurrence: chronic infection, cancer
Features:
(1) functional (qualitative) defect of T-cells (CD8+, CD4+)
(2) low proliferative response to antigen stimulation
(3) progressive loss of cytokine production and killing function
(4) expression of multiple inhibitory receptors (PD-1, CTLA-4, Tim-3, LAG3, CD39, other)
(5) metabolic defects (reduced oxidative phosphorylation, altered glycolysis)
Exhausted T-cells can be rejuvenated if the underlying cause is addressed, such as blocking of inhibitory receptors.
Differential diagnosis:
(1) lymphopenia (quantitative deficiency in lymphocytes)
(2) other causes of immunodeficiency
