Regulatory T-Cell Development in the Human Thymus.
The thymus generates a lineage-committed subset of regulatory T-cells (Tregs), best identified by the expression of the transcription factor FOXP3. The development of thymus-derived Tregs is known to require high-avidity interaction with MHC-self peptides leading to the generation of self-reactive Tregs fundamental for the maintenance of self-tolerance. Notwithstanding their crucial role in the control of immune responses, human thymic Treg differentiation remains poorly understood. In this mini-review, we will focus on the developmental stages at which Treg lineage commitment occurs, and their spatial localization in the human thymus, reviewing the molecular requirements, including T-cell receptor and cytokine signaling, as well as the cellular interactions involved. An overview of the impact of described thymic defects on the Treg compartment will be provided, illustrating the importance of these in vivo models to investigate human Treg development.
Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa , Lisbon , Portugal.
Íris
Í
Caramalho
Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa , Lisbon , Portugal.
Helena
H
Nunes-Cabaço
Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa , Lisbon , Portugal.
Russell B
RB
Foxall
Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa , Lisbon , Portugal.
Ana E
AE
Sousa
FOXP3; human thymic defects; human thymus; primary immunodeficiency; regulatory T-cell development; regulatory T-cells