A Mathematical Model of the Effects of Aging on Naive T Cell Populations and Diversity

  • Stephanie Lewkiewicz
  • Yao-li Chuang
  • Tom ChouEmail author


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.


Immunosenescence T cell Aging Diversity Thymus 



This work was supported by the NIH via Grants R56HL126544 (SL) and R01HL146552 (TC), the NSF via Grants R56HL126544 (TC), and the Army Research Office (YLC, W1911NF14-1-0472).

Supplementary material


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Copyright information

© Society for Mathematical Biology 2019

Authors and Affiliations

  1. 1.Department of MathematicsUCLALos AngelesUSA
  2. 2.Department of MathematicsCalState-NorthridgeNorthridgeUSA
  3. 3.Department of BiomathematicsUCLALos AngelesUSA

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