Human FOXN1 Deficiency Is Associated with Alpha Beta Double-Negative and FoxP3 Positive T-Cell Expansions That Are Distinctly Modulated upon Thymic Transplantation

    May 2012 in “ PloS one ”
    Adriana S. Albuquerque, José Gonçalo Marques, Susana L. Silva, Dário Ligeiro, Blythe H. Devlin, Jacques Dutrieux, Rémi Cheynier, Claudio Pignata, Rui M. M. Victorino, M. Louise Markert, Ana E. Sousa
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    TLDR Thymic transplantation normalized some T-cells but not others, maintaining immune function.
    A study on a patient with a rare homozygous FOXN1 mutation (R255X) causing alopecia universalis and thymus aplasia revealed unexpected non-maternal circulating T-cells and large numbers of aberrant double-negative αβ T-cells (CD4negCD8neg, DN) and regulatory-like T-cells. This suggested the presence of a thymic rudiment allowing disturbed T-cell development. Post HLA-mismatched thymic transplantation, regulatory-like T-cell numbers normalized, but the αβDN subset persisted 5 years later. Despite thymus allograft involution 3 years post-transplantation, functional immune competence was maintained, offering insights for immunological reconstitution strategies using thymic transplantation.
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