Browse by author
Lookup NU author(s): Dr Jeroen Stoop, Professor Jelena Mann, Steven Woods, Anne Kozijn, Professor Sophie HambletonORCiD, Professor John Robinson, Professor John IsaacsORCiD, Dr Amy AndersonORCiD, Professor Catharien Hilkens
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
We show that the strength of T-cell stimulation determines the capability of human CD4(+) T cells to become interleukin-17 (IL-17) producers. CD4(+) T cells received either high-(THi) or low (TLo)-strength stimulation via anti-CD3/CD28 beads or dendritic cells pulsed with superantigen in the presence of pro-Th17 cytokines IL-1 beta, transforming growth factor beta, and IL-23. We found that TLo, but not THi, stimulation profoundly promoted Th17 responses by enhancing both the relative proportion and total number of Th17 cells. Titration of anti-CD3 revealed that low TCR signaling promoted Th17 cells, but only in the presence of anti-CD28. Impaired IL-17 production in THi cells could not be explained by high levels of Foxp3 or transforming growth factor beta-latency-associated peptide expressed by THi cells. Nuclear factor of activated T cells was translocated to the nucleus in both THi and TLo cells, but only bound to the proximal region of the IL-17 promoter in TLo cells. The addition of a Ca2+ ionophore under TLo conditions reversed the pro-Th17 effect, suggesting that high Ca2+ signaling impairs Th17 development. Although our data do not distinguish between priming of naive T cells versus expansion/differentiation of memory T cells, our results clearly establish an important role for the strength of T-cell activation in regulating Th17 responses. (Blood. 2010;116(23):4829-4837)
Author(s): Purvis HA, Stoop JN, Mann J, Woods S, Kozijn AE, Hambleton S, Robinson JH, Isaacs JD, Anderson AE, Hilkens CMU
Publication type: Article
Publication status: Published
Journal: Blood
Year: 2010
Volume: 116
Issue: 23
Pages: 4829-4837
Print publication date: 01/12/2010
ISSN (print): 0006-4971
ISSN (electronic): 1528-0020
Publisher: American Society of Hematology
URL: http://dx.doi.org/10.1182/blood-2010-03-272153
DOI: 10.1182/blood-2010-03-272153
Altmetrics provided by Altmetric
