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

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## Abstract

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.

## Keywords

Immunosenescence T cell Aging Diversity Thymus## Notes

### Acknowledgements

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

## References

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