  The human adaptive immune response is known to weaken in advanced age,
resulting in increased severity of pathogen-born illness, poor vaccine
efficacy, and a higher prevalence of cancer in the elderly. Age-related erosion
of the T-cell compartment has been implicated as a likely cause, but the
underlying mechanisms driving this immunosenescence have not been
quantitatively modeled and systematically analyzed. T-cell receptor diversity,
or the extent of pathogen-derived antigen responsiveness of the T-cell pool, is
known to diminish with age, but inherent experimental difficulties preclude
accurate analysis on the full organismal level. In this paper, we formulate a
mechanistic mathematical model of T-cell population dynamics on the
immunoclonal subpopulation level, which provides quantitative estimates of
diversity. We define different estimates for diversity that depend on the
individual number of cells in a specific immunoclone. We show that diversity
decreases with age primarily due to diminished thymic output of new T-cells and
the resulting overall loss of small immunoclones.
