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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.


Naive CD4 T cell concentrations (cells/μl of blood) predicted by the model for children aged 0–3 years (red curve) compared with clinical data for normal children.
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Figure 6: Naive CD4 T cell concentrations (cells/μl of blood) predicted by the model for children aged 0–3 years (red curve) compared with clinical data for normal children.

Mentions: Having established the behavior of the two-compartment model for naive CD4 T cell homeostasis in adults, we sought to determine whether it could also be used to explain the changes in T cell numbers that occur during childhood. During the first few years of life as thymic output changes and children grow, the naive CD4 T cell concentration decreases while the total number increases (Figure 1). The question is whether the homeostatic mechanism described by the model is in itself enough to explain these variations, or whether different and changing mechanisms apply in children. To examine this question, the model was used to predict the concentration of naive CD4 T cells in cells/μl of blood by converting total numbers to concentration using the estimated blood volume of children at different ages (14). In addition, the changes in thymic output that occur over the first few years of life with a peak at 1 year and then a decline (15) were incorporated into the model. The prediction from the model was then simply compared without parameter fitting to data collected from a cohort of healthy children (born to HIV infected mothers) from the European Collaborative Study on HIV infected pregnant women and their children (28) (Figure 6). As can be seen, the model predicted the concentration of T cells over the first 3 years of life extremely well suggesting that the homeostatic mechanisms in children and adults are essentially the same with the only difference being thymic output and growth with a concomitant increase in blood volume.


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

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

Naive CD4 T cell concentrations (cells/μl of blood) predicted by the model for children aged 0–3 years (red curve) compared with clinical data for normal children.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 6: Naive CD4 T cell concentrations (cells/μl of blood) predicted by the model for children aged 0–3 years (red curve) compared with clinical data for normal children.
Mentions: Having established the behavior of the two-compartment model for naive CD4 T cell homeostasis in adults, we sought to determine whether it could also be used to explain the changes in T cell numbers that occur during childhood. During the first few years of life as thymic output changes and children grow, the naive CD4 T cell concentration decreases while the total number increases (Figure 1). The question is whether the homeostatic mechanism described by the model is in itself enough to explain these variations, or whether different and changing mechanisms apply in children. To examine this question, the model was used to predict the concentration of naive CD4 T cells in cells/μl of blood by converting total numbers to concentration using the estimated blood volume of children at different ages (14). In addition, the changes in thymic output that occur over the first few years of life with a peak at 1 year and then a decline (15) were incorporated into the model. The prediction from the model was then simply compared without parameter fitting to data collected from a cohort of healthy children (born to HIV infected mothers) from the European Collaborative Study on HIV infected pregnant women and their children (28) (Figure 6). As can be seen, the model predicted the concentration of T cells over the first 3 years of life extremely well suggesting that the homeostatic mechanisms in children and adults are essentially the same with the only difference being thymic output and growth with a concomitant increase in blood volume.

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.