File:DiGeorge T cell receptor Diversity post thymus transplant.jpg

Figure 1. Clone sizes, T cell concentrations and TCR repertoire diversity.

Clone sizes over time as computed under the model of Eqs.(1,4) (A–C) and the corresponding T cell concentrations (D) and TCR repertoire diversity (E) as a function of time past transplantation. computed under the model of Eqs.(1,4) as a function of time past transplantation. Parameter (see Model section) is varied as indicated while all other parameters are held constant. The higher , the more limiting are TCR-specific resources. “Emigrant number” refers to the order in which clones leave the thymus and enter the periphery; emigrant number 1 is the first clone to arise, etc. doi:10.1371/journal.pcbi.1000396.g001

Thymus transplantation is emerging as a valuable treatment for athymia generally. There is therefore substantial medical interest in elucidating the immunological recovery of thymus transplant patients quite apart from the basic immunology these patients may reveal.

To illustrate the connection between these alternative homeostatic mechanisms and the observations one might make on the DiGeorge subjects, consider the following two scenarios as a thought experiment. First, suppose that TCR-specific resources such as spMHC are not limiting, either because they are produced in great excess or because they are rendered unnecessary. Under these conditions, homeostasis will be due exclusively to competition for TCR-nonspecific resources. The first T cells leaving the thymus will expand rapidly, consuming the TCR-nonspecific resources required for growth of their own growth and for the growth of all other clones. Subsequent T cells leaving the thymus will encounter a more impoverished environment and will grow more slowly, leading to early dominance of one or a small number of early clones and therefore a limited TCR repertoire (Figure 1). Conversely, if TCR-nonspecific resources such as cytokines were not limiting, and that homeostasis therefore depended solely on competition for TCR-specific signaling, the only cellular competition would be among T cells of the same clonotype. In this case, each clone will grow to roughly the same self-limiting size regardless of when its founder emigrates from the thymus. In this case, TCR repertoire diversity will grow at the greatest possible rate, all other things being equal (Figure 1).

Copyright: © 2009 Ciupe et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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