Description:
<jats:title>Abstract</jats:title>
<jats:p>CD4+CD25+ T regulatory lymphocytes (Tregs) play an important role in maintaining immune homeostasis and require IL-2 for their development, expansion, maintenance, and function. Because Tregs do not produce IL-2, they must obtain it from a paracrine source. The identity of a cell providing IL-2 to Tregs is controversial, and the manner in which IL-2 is delivered to Tregs is not well understood. We found that Treg in vitro inhibitory function depends on IL-2 produced by dendritic cells (DCs). By confocal microscopy of in vitro cultures we documented that CD25 (IL-2Rα) concentrated at the JAWSII (DC hybridoma) - RD6 (Treg hybridoma) contact sites, internalized DC material co-localized with CD25 in the RD6, and Tregs internalized IL-2 from transfected DCs. Tregs cultured with WT, but not IL-2 KO DCs, up-regulated CD25 and Foxp3 in contact-dependent manner. To examine IL-2 trafficking between DCs and T cells we examined co-cultures of IL-2mCherry transfected DCs and Treg or T effector cells. DC-Treg contact significantly enhanced IL-2 uptake by Tregs and resulted in up-regulation of CD25 on Tregs. In contrast, Teffs did not acquire IL-2 from DCs in culture. Altogether, these data suggest that 1) DCs are an important source of IL-2 for Tregs, and 2) delivery of IL-2 from DCs to Tregs is Treg-specific and facilitated by close cell-cell contact. These novel findings may further our understanding of requirements for Treg biology during the homeostatic maintenance and immune response.</jats:p>