A 33D1(+) Dendritic Cell/Autoreactive CD4(+) T Cell Circuitn Maintains IL-2-Dependent Regulatory T Cells in the Spleen

作者：Stolley J Michael; Campbell Daniel J

来源：The Journal of Immunology, 2016, 197(7): 2635-2645.

DOI：10.4049/jimmunol.1600974

Phenotypically and functionally diverse regulatory T (T-r) cell subsets populate lymphoid and nonlymphoid tissues, where their maintenance and function are governed by unique homeostatic signals. Whereas T-r cells resident in nonlymphoid tissues depend on continual TCR signaling for their survival and function, phenotypically naive T-r cells occupying secondary lymphoid organs are largely supported by paracrine IL-2 signaling. Crucially, the absence of either of these distinct T-r cell subsets results in pathogenic autoimmunity, underscoring their nonredundant roles in the preservation of self-tolerance. However, the cellular and molecular factors precipitating IL-2 release and subsequent maintenance of secondary lymphoid organ-resident T-r cells are still poorly understood. In this study, we report that IL-2-dependent T-r cells in the spleen compete for a limiting supply of paracrine IL-2 generated by autoreactive CD4(+) T cells in response to MHC class II-restricted autoantigen activation by 33D1(+)CD11b(int) dendritic cells. Manipulating this cellular circuit culminating in IL-2 production could have clinical benefits in settings in which diminished T-r cell abundance is desired.

• 出版日期2016-10-1