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A mechanistic model for naive CD4 T cell homeostasis in healthy adults and children.

Hapuarachchi T, Lewis J, Callard RE - Front Immunol (2013)

Bottom Line: Thymic output increases in the first year of life and then decreases but is crucial for establishing repertoire diversity.The model successfully predicts the homeostatic set point for T cells in adults and identifies variables that determine the total number of T cells.It also accurately predicts T cell numbers in children in early life despite rapid changes in thymic output and growth over this period.

View Article: PubMed Central - PubMed

Affiliation: Institute of Child Health and CoMPLEX, University College London , London , UK.

ABSTRACT
The size and composition of the T lymphocyte compartment is subject to strict homeostatic regulation and is remarkably stable throughout life in spite of variable dynamics in cell production and death during T cell development and immune responses. Homeostasis is achieved by careful orchestration of lymphocyte survival and cell division. New T cells are generated from the thymus and the number of peripheral T cells is regulated by controlling survival and proliferation. How these processes combine is however very complex. Thymic output increases in the first year of life and then decreases but is crucial for establishing repertoire diversity. Proliferation of new naive T cells plays a crucial role for maintaining numbers but at a potential cost to TCR repertoire diversity. A mechanistic two-compartment model of T cell homeostasis is described here that includes specific terms for thymic output, cell proliferation, and cell death of both resting and dividing cells. The model successfully predicts the homeostatic set point for T cells in adults and identifies variables that determine the total number of T cells. It also accurately predicts T cell numbers in children in early life despite rapid changes in thymic output and growth over this period.

No MeSH data available.


Ratio of dividing to resting cells predicted by the model. Starting with 0.01 × 1011 (blue curve) or 2 × 1011 (red curve) the approximate ratio of dividing to resting cells changes over time to reach an equilibrium of about 0.4%. As expected, the proportion of proliferating cells is greater when the initial cell number is low. Parameter values used in the model are the same as in Figure 3.
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Figure 4: Ratio of dividing to resting cells predicted by the model. Starting with 0.01 × 1011 (blue curve) or 2 × 1011 (red curve) the approximate ratio of dividing to resting cells changes over time to reach an equilibrium of about 0.4%. As expected, the proportion of proliferating cells is greater when the initial cell number is low. Parameter values used in the model are the same as in Figure 3.

Mentions: The ratio of dividing to resting cells is shown in Figure 4. With lymphopenic starting conditions of 0.01 (×1011) resting cells, the proportion of proliferating cells (blue curve) increased very rapidly from 0 to 0.013 and then slowly declined over about 200 days to reach an equilibrium at about 0.5%. In contrast, under starting conditions of excessive T cells, the ratio of dividing to non-dividing cells increased rapidly at first from 0 to about 0.2% and then slowly to reach the same equilibrium of about 0.5%. This equilibrium point is consistent with a low level of cell division in the naive compartment of adult humans as reported previously (25, 26).


A mechanistic model for naive CD4 T cell homeostasis in healthy adults and children.

Hapuarachchi T, Lewis J, Callard RE - Front Immunol (2013)

Ratio of dividing to resting cells predicted by the model. Starting with 0.01 × 1011 (blue curve) or 2 × 1011 (red curve) the approximate ratio of dividing to resting cells changes over time to reach an equilibrium of about 0.4%. As expected, the proportion of proliferating cells is greater when the initial cell number is low. Parameter values used in the model are the same as in Figure 3.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3822783&req=5

Figure 4: Ratio of dividing to resting cells predicted by the model. Starting with 0.01 × 1011 (blue curve) or 2 × 1011 (red curve) the approximate ratio of dividing to resting cells changes over time to reach an equilibrium of about 0.4%. As expected, the proportion of proliferating cells is greater when the initial cell number is low. Parameter values used in the model are the same as in Figure 3.
Mentions: The ratio of dividing to resting cells is shown in Figure 4. With lymphopenic starting conditions of 0.01 (×1011) resting cells, the proportion of proliferating cells (blue curve) increased very rapidly from 0 to 0.013 and then slowly declined over about 200 days to reach an equilibrium at about 0.5%. In contrast, under starting conditions of excessive T cells, the ratio of dividing to non-dividing cells increased rapidly at first from 0 to about 0.2% and then slowly to reach the same equilibrium of about 0.5%. This equilibrium point is consistent with a low level of cell division in the naive compartment of adult humans as reported previously (25, 26).

Bottom Line: Thymic output increases in the first year of life and then decreases but is crucial for establishing repertoire diversity.The model successfully predicts the homeostatic set point for T cells in adults and identifies variables that determine the total number of T cells.It also accurately predicts T cell numbers in children in early life despite rapid changes in thymic output and growth over this period.

View Article: PubMed Central - PubMed

Affiliation: Institute of Child Health and CoMPLEX, University College London , London , UK.

ABSTRACT
The size and composition of the T lymphocyte compartment is subject to strict homeostatic regulation and is remarkably stable throughout life in spite of variable dynamics in cell production and death during T cell development and immune responses. Homeostasis is achieved by careful orchestration of lymphocyte survival and cell division. New T cells are generated from the thymus and the number of peripheral T cells is regulated by controlling survival and proliferation. How these processes combine is however very complex. Thymic output increases in the first year of life and then decreases but is crucial for establishing repertoire diversity. Proliferation of new naive T cells plays a crucial role for maintaining numbers but at a potential cost to TCR repertoire diversity. A mechanistic two-compartment model of T cell homeostasis is described here that includes specific terms for thymic output, cell proliferation, and cell death of both resting and dividing cells. The model successfully predicts the homeostatic set point for T cells in adults and identifies variables that determine the total number of T cells. It also accurately predicts T cell numbers in children in early life despite rapid changes in thymic output and growth over this period.

No MeSH data available.