  Complete understanding of the mechanisms regulating the proliferation and
differentiation that takes place during human immune CD8+ T cell responses is
still lacking. Human clinical data is usually limited to blood cell counts, yet
the initiation of these responses occurs in the draining lymph nodes;
antigen-specific effector and memory CD8+ T cells generated in the lymph nodes
migrate to those tissues where they are required. We use approximate Bayesian
computation with deterministic mathematical models of CD8+ T cell populations
(naive, central memory, effector memory and effector) and yellow fever virus
vaccine data to infer the dynamics of these CD8+ T cell populations in three
spatial compartments: draining lymph nodes, circulation and skin. We have made
use of the literature to obtain rates of division and death for human CD8+ T
cell population subsets and thymic export rates. Under the decreasing potential
hypothesis for differentiation during an immune response, we find that, as the
number of T cell clonotypes driven to an immune response increases, there is a
reduction in the number of divisions required to differentiate from a naive to
an effector CD8+ T cell, supporting the "division of labour" hypothesis
observed in murine studies. We have also considered the reverse differentiation
scenario, the increasing potential hypothesis. The decreasing potential model
is better supported by the yellow fever virus vaccine data.
