We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Naive and activated T cells display differential responsiveness to TL1A that affects Th17 generation, maintenance, and proliferation.
- Authors
Jones, Gareth W.; Stumhofer, Jason S.; Foster, Tom; Twohig, Jason P.; Hertzog, Paul; Topley, Nicholas; Williams, Anwen S.; Hunter, Christopher A.; Jenkins, Brendan J.; Wang, Eddie C. Y.; Jones, Simon A.
- Abstract
Tumor necrosis factor (TNF)-like cyto-kine (TL1A) is a T-cell costimulator that bolsters cyto- kine-induced activation through death receptor 3 (DR3). To explore the relationship between T-cell activation and TL1A responsiveness, flow cytometry profiled DR3 expression in resting and activated T cells. In human CD4+ T cells, DR3 was induced rapidly following activation and expressed prominently by in-terleukin (IL)-17-secreting T cells (Thl7). Splenic T cells from wild-type and DR3-deficient mice showed that TL1A activation of DR3 inhibits Thl7 generation (81 ± 2.6% at 100 ng/ml TL1A) from naive T cells. This response was not associated with suppression of T-cell proliferation. Using neutralizing antibodies or T cells derived from genetically modified mice, TL1A inhibition of Th17 development was found to be independent of IL-2, IL-27, γFN, IFNAR1, and STAT1. 17A secretion, however, the reduced threshold of Under suboptimal TCR activation, TL1A continued to block IL-17A secretion, however, the reduced threshold of TCR engagement was now linked with an increase in TL1A-driven proliferation. In contrast, fully committed Thl7 cells displayed an altered TL1A responsiveness and in the absence of TCR costimulation supported the maintenance of T cell IL-17A expression. Consequently, TL1A orchestrates unique outcomes in naive and effector T-helper cells, which may affect the proliferation, differentiation and maintenance of Thl7 cells in peripheral compartments and inflamed tissues.
- Subjects
TUMOR necrosis factors; T cells; DEATH receptors; FLOW cytometry; INTERLEUKIN-2; CELLS
- Publication
FASEB Journal, 2011, Vol 25, Issue 1, p409
- ISSN
0892-6638
- Publication type
Article
- DOI
10.1096/fj.10-166843