A regenerative perspective on successful and failed T-cell immunity

Abstract

Heightened immunity after a primary infection, persistent control of low-level infection, or vanquished immunity from chronic-active infection and cancer are interrelated issues concerning the nature of T-cell regeneration during immunity. For many regenerating tissues and cellular systems, such as epithelia and blood, there are at least three distinguishable stages of development and repair, marked by progressive loss of self-renewal and progressive commitment to differentiation. T cells seem to be no different. Quiescent precursors become activated and yield anabolic, proliferative progenitors while self-renewing the quiescent precursor population. Activated progenitors then yield differentiated cellular descendants alongside the self-renewal of progenitors. Nomenclature reflecting the mutually opposing nature of T-cell self-renewal and T-cell differentiation would help synchronize phenomena such as T-cell memory, protective immunity, and T-cell exhaustion with other regenerative paradigms, as well as offer new strategies to influence the intensity and duration of immunity.