T Cell Exhaustion Dynamics

Persistent antigen drives effector → exhausted transition; PD-1 reinvigoration

Antigen persistence α: 0.50
Exhaustion rate κ: 0.30
PD-1 blockade β: 0.00
Viral clearance γ: 0.10

T cell exhaustion (Wherry 2011): During chronic infection, repeated TCR stimulation drives T cells from effector (high cytokine, high killing) to exhausted state (PD-1hi, low function). Model: dE/dt = s + β·X - (δ_E + κ·V)·E | dX/dt = κ·V·E - (δ_X + β)·X | dV/dt = α·V - γ·E·V PD-1 blockade (β) reinvigorates exhausted cells → restored effector function (clinical basis for checkpoint immunotherapy).

T Cell Exhaustion in Chronic Infection