The dynamics of T-cell receptor repertoire diversity following thymus transplantation for DiGeorge anomaly

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Abstract

Author Summary<br />Protective adaptive immunity depends crucially on the enormous diversity of the<br />T-cell receptor repertoire, the antigen receptors expressed collectively on<br />T-cell populations. T cells develop from T-cell precursors that originate in the<br />bone marrow and migrate to the thymus, where their T cell receptors are<br />constructed stochastically, and tested for autoreactivity against a host of self<br />antigens. Complete DiGeorge anomaly is a rare congenital disease in which the<br />thymus fails to develop, blocking all T cell development and causing profound<br />immunodeficiency. Thymus transplantation, performed in the first two post-natal<br />years, allows the patient's own T cell precursors to develop in the<br />engrafted thymus tissue into normal, functioning T cells. In addition to saving<br />patients' lives, this procedure provides an extraordinary opportunity<br />to study the de novo development of human T cell populations.<br />We have developed a mathematical model to aid in the statistical analysis of the<br />precious data from these patients. In addition to helping elucidate the means by<br />which the size and diversity of T cell populations are jointly regulated, the<br />insights gained from this study hold promise for the development of therapies to<br />promote immune recovery after transplantation.

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Ciupe, S. M., Devlin, B. H., Markert, M. L., & Kepler, T. B. (2009). The dynamics of T-cell receptor repertoire diversity following thymus transplantation for DiGeorge anomaly. PLoS Computational Biology, 5(6). https://doi.org/10.1371/journal.pcbi.1000396

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