Modelling the Dynamics of T-Cell Development in the Thymus

Abstract

The thymus hosts the development of a specific type of adaptive immune cells called T cells. T cells orchestrate the adaptive immune response through recognition of antigen by the highly variable T-cell receptor (TCR). T-cell development is a tightly coordinated process comprising lineage commitment, somatic recombination of Tcr gene loci and selection for functional, but non-self-reactive TCRs, all interspersed with massive proliferation and cell death. Thus, the thymus produces a pool of T cells throughout life capable of responding to virtually any exogenous attack while preserving the body through self-tolerance. The thymus has been of considerable interest to both immunologists and theoretical biologists due to its multiscale quantitative properties, bridging molecular binding, population dynamics and polyclonal repertoire specificity. Here, we review mathematical modelling strategies that were reported to help understand the flexible dynamics of the highly dividing and dying thymic cell populations. Furthermore, we summarize the current challenges to estimating in vivo cellular dynamics and to reaching a next-generation multiscale picture of T-cell development.

Metabolic Reprogramming Driven by Ant2 -Targeting Augments T-Cell Function and Anti-Tumor Immunity

“…Comparing WT and Ant2 -/mice, we found that the pre-and postpositive selection thymic populations, CD69 -TCRβand CD69 + TCRβ hi , respectively, were comparable between the two groups (Figure 1C-D). 23 However, we observed a slight but significant decrease in the double-positive (CD4 + CD8 + ) cell population and an increase in the single-positive (CD4 + or CD8 + ) cell populations in Ant2 -/mice (Figure 1E-F). These findings suggest intact thymic development with a minor increase in thymic egress, which is consistent with the observed T-cell lymphopenia in Ant2 -/mice.…”