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Human FOXN1-deficiency is associated with ?? double-negative and FoxP3+ T-cell expansions that are distinctly modulated upon thymic transplantation.


ABSTRACT: Forkhead box N1 (FOXN1) is a transcription factor crucial for thymic epithelium development and prevention of its involution. Investigation of a patient with a rare homozygous FOXN1 mutation (R255X), leading to alopecia universalis and thymus aplasia, unexpectedly revealed non-maternal circulating T-cells, and, strikingly, large numbers of aberrant double-negative ?? T-cells (CD4negCD8neg, DN) and regulatory-like T-cells. These data raise the possibility that a thymic rudiment persisted, allowing T-cell development, albeit with disturbances in positive/negative selection, as suggested by DN and FoxP3+ cell expansions. Although regulatory-like T-cell numbers normalized following HLA-mismatched thymic transplantation, the ??DN subset persisted 5 years post-transplantation. Involution of thymus allograft likely occurred 3 years post-transplantation based on sj/?TREC ratio, which estimates intrathymic precursor T-cell divisions and, consequently, thymic explant output. Nevertheless, functional immune-competence was sustained, providing new insights for the design of immunological reconstitution strategies based on thymic transplantation, with potential applications in other clinical settings.

SUBMITTER: Albuquerque AS 

PROVIDER: S-EPMC3349657 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Human FOXN1-deficiency is associated with αβ double-negative and FoxP3+ T-cell expansions that are distinctly modulated upon thymic transplantation.

Albuquerque Adriana S AS   Albuquerque Adriana S AS   Marques José G JG   Silva Susana L SL   Ligeiro Dario D   Devlin Blythe H BH   Dutrieux Jacques J   Cheynier Rémi R   Pignata Claudio C   Victorino Rui M M RM   Markert M Louise ML   Sousa Ana E AE  

PloS one 20120510 5


Forkhead box N1 (FOXN1) is a transcription factor crucial for thymic epithelium development and prevention of its involution. Investigation of a patient with a rare homozygous FOXN1 mutation (R255X), leading to alopecia universalis and thymus aplasia, unexpectedly revealed non-maternal circulating T-cells, and, strikingly, large numbers of aberrant double-negative αβ T-cells (CD4negCD8neg, DN) and regulatory-like T-cells. These data raise the possibility that a thymic rudiment persisted, allowin  ...[more]

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