The plasticity of regulatory T cell function

Meenu R. Pillai, Lauren W. Collison, Xiaohua Wang, David Finkelstein, Jerold E. Rehg, Kelli Boyd, Andrea L. Szymczak-Workman, Teresa Doggett, Thomas S. Griffith, Thomas A. Ferguson, Dario A.A. Vignali

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47 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)4987-4997
Number of pages11
JournalJournal of Immunology
Volume187
Issue number10
DOIs
StatePublished - Nov 15 2011

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    Pillai, M. R., Collison, L. W., Wang, X., Finkelstein, D., Rehg, J. E., Boyd, K., Szymczak-Workman, A. L., Doggett, T., Griffith, T. S., Ferguson, T. A., & Vignali, D. A. A. (2011). The plasticity of regulatory T cell function. Journal of Immunology, 187(10), 4987-4997. https://doi.org/10.4049/jimmunol.1102173