Kelli Boyd
Faculty Member
Last active: 3/20/2014

The plasticity of regulatory T cell function.

Pillai MR, Collison LW, Wang X, Finkelstein D, Rehg JE, Boyd K, Szymczak-Workman AL, Doggett T, Griffith TS, Ferguson TA, Vignali DA
J Immunol. 2011 187 (10): 4987-97

PMID: 22013112 · PMCID: PMC3208127 · DOI:10.4049/jimmunol.1102173

Regulatory T cells (T(regs)) can suppress a wide variety of cell types, in diverse organ sites and inflammatory conditions. Whereas T(regs) possess multiple suppressive mechanisms, the number required for maximal function is unclear. Furthermore, whether any interrelationship or cross-regulatory mechanisms exist to orchestrate and control their utilization is unknown. In this study, we assessed the functional capacity of T(regs) lacking the ability to secrete both IL-10 and IL-35, which individually are required for maximal T(reg) activity. Surprisingly, IL-10/IL-35 double-deficient T(regs) were fully functional in vitro and in vivo. Loss of IL-10 and IL-35 was compensated for by a concurrent increase in cathepsin E (Ctse) expression, enhanced TRAIL (Tnfsf10) expression, and soluble TRAIL release, rendering IL-10/IL-35 double-deficient T(regs) functionally dependent on TRAIL in vitro and in vivo. Lastly, whereas C57BL/6 T(regs) are normally IL-10/IL-35 dependent, BALB/c T(regs), which express high levels of cathepsin E and enhanced TRAIL expression, are partially TRAIL dependent by default. These data reveal that cross-regulatory pathways exist that control the utilization of suppressive mechanisms, thereby providing T(reg) functional plasticity.

MeSH Terms (15)

Animals Cathepsin E Cells, Cultured Coculture Techniques Down-Regulation HEK293 Cells Humans Interleukin-10 Interleukins Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Knockout T-Lymphocytes, Regulatory TNF-Related Apoptosis-Inducing Ligand

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