Lymphotoxin limits Foxp3 regulatory T cell development from Foxp3 precursors via IL-4 signaling.

Regulatory T cells (T) are critical players of immune tolerance that develop in the thymus via two distinct developmental pathways involving CD25Foxp3 and CD25Foxp3 precursors. However, the mechanisms regulating the recently identified Foxp3 precursor pathway remain unclear. Here, we find that the membrane-bound lymphotoxin αβ (LTαβ) heterocomplex is upregulated during T development upon TCR/CD28 and IL-2 stimulation.

IL-2 and IL-15 drive intrathymic development of distinct periphery-seeding CD4Foxp3 regulatory T lymphocytes.

Development of Foxp3-expressing regulatory T-lymphocytes (Treg) in the thymus is controlled by signals delivered in T-cell precursors the TCR, co-stimulatory receptors, and cytokine receptors. In absence of IL-2, IL-15 or their receptors, fewer Treg apparently develop in the thymus. However, it was recently shown that a substantial part of thymic Treg are cells that had recirculated from the periphery back to the thymus, troubling interpretation of these results.

IL-2 and IL-15 dependent thymic development of Foxp3-expressing regulatory T lymphocytes.

Immunosuppressive regulatory T lymphocytes (Treg) expressing the transcription factor Foxp3 play a vital role in the maintenance of tolerance of the immune-system to self and innocuous non-self. Most Treg that are critical for the maintenance of tolerance to self, develop as an independent T-cell lineage from common T cell precursors in the thymus. In this organ, their differentiation requires signals from the T cell receptor for antigen, from co-stimulatory molecules, as well as from cytokine-receptors.