Population mechanics: A mathematical framework to study T cell homeostasis

Area of Science:

• Immunology
• Theoretical Biology
• Computational Biology

Background:

• T cells lack tissue structure, moving independently and facing a diversity paradox due to resource competition.
• Classical population dynamics struggle to reconcile resource competition with high T cell clone diversity.

Purpose of the Study:

• To apply population mechanics to T cell homeostasis, explaining clone diversity through interleukin competition.
• To model how carrying capacities emerge from interleukin dynamics in T cell populations.

Main Methods:

• Utilizing population mechanics, a non-standard theoretical approach.
• Developing models based on interleukin production and consumption dynamics.
• Analyzing differences in diversity maintenance between naive and memory T cell pools.

Main Results:

• Carrying capacities for T cell populations naturally arise from the balance of interleukin production and consumption.
• Distinct mechanisms govern diversity in naive (antigen affinity) and memory (recent activation/threat) T cell pools.
• Memory T cell distribution favors clones responding to recent or aggressive threats.

Conclusions:

• Population mechanics provides a framework for understanding T cell homeostasis and diversity.
• Naive T cell clone permanence is linked to antigen affinity, while memory T cell selection is driven by activation history and threat.
• Positive and negative selection are interpreted as strategies to maximize naive T cell diversity.