Multifunctional Regulatory T Cells from Human Umbilical Cord Blood and the Role of Tumor Necrosis Factor in Immune Homeostasis

Regulatory T cells (Tregs) are required to suppress inflammation and prevent autoimmunity. During fetal development Tregs are crucial to maintain tolerance between mother and child. After birth, neonates require tolerance to avoid harmful immune responses to foreign antigens in food and allow colonization with commensal microbes. We demonstrate a propensity for T cells in human umbilical cord blood to differentiate into Tregs in response to antigen receptor stimulation ex vivo. Cord blood-derived Tregs potently suppress T cell proliferation, but also produce pro-inflammatory cytokines known to activate innate immune responses. These results suggest that antigen exposure during early life results in development of T cells with both regulatory and effector functions. Surprisingly, we observe expression of tumor necrosis factor (TNF) by cord blood and adult Tregs. We show a role for autocrine TNF signaling in survival of Tregs, suggesting an important function for TNF in immune tolerance and homeostasis.