Human FOXN1-Deficiency Is Associated with αβ Double-Negative and FoxP3+ T-Cell Expansions That Are Distinctly Modulated upon Thymic Transplantation
by Adriana S. Albuquerque, José G. Marques, Susana L. Silva, Dario Ligeiro, Blythe H. Devlin, Jacques Dutrieux, Rémi Cheynier, Claudio Pignata, Rui M. M. Victorino, M. Louise Markert, Ana E. Sousa
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, 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 αβDN subset persisted 5 years post-transplantation. Involution of thymus allograft likely occurred 3 years post-transplantation based on sj/βTREC 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.
For the full article visit: Human FOXN1-Deficiency Is Associated with αβ Double-Negative and FoxP3+ T-Cell Expansions That Are Distinctly Modulated upon Thymic Transplantation
Syndicated from:PLoS ONE
Article is licensed under a Creative Commons Attribution License.