Anti-CD28-induced co-stimulation and TCR avidity regulates the differential effect of TGF-beta1 on CD4+ and CD8+ naïve human T-cells
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
MetadataShow full item record
CitationInt. Immunol. 2005, 17(1):35-44
AbstractTGF-beta1 is a powerful regulator of various T-cell functions. However, it has been unclear how the T-cell responsiveness towards TGF-beta1 is affected by its phenotype or signaling intensity. In the present study, we demonstrate that the phenotype and the TCR-signaling intensity of the responding T-cell as well as the presence of anti-CD28 co-stimulation markedly affects how naïve human cord blood T-cells respond to TGF-beta1. In this report we demonstrate that the strength of the stimulatory signal modifies the T-cell response towards TGF-beta1. Thus, the greatest anti-proliferative effect of TGF-beta1 was observed during weak stimulatory conditions (low dose of anti-CD3 with no co-stimulatory signal). However, such anti-proliferative effect was reduced during strong stimulatory signal (high dose of anti-CD3 with a CD28-directed co-stimulatory signal). In addition, our results indicate that CD8+ T-cells are generally more responsive towards TGF-beta1 than CD4+ T-cells. To our surprise, naïve T-cells had a skewed Th1/Tc1 cytokine secretion pattern with high amounts of IL-2, IFNgamma and TNFalpha, but low amounts of IL-4, IL-5 and IL-10. TGFbeta1 significantly reduced the secretion of IL-2 and IFNgamma, but such suppression was partially prevented by anti-CD28-induced co-stimulation. In contrast, the inhibitory effect on IL-5 secretion was unaffected by anti-CD28 co-stimulation. Interestingly, TGF-beta1 induced IL-10 and TNFalpha secretion. However, the induction of IL-10 secretion was reduced during optimal stimulatory conditions while TGF-beta1 further induced TNFalpha secretion. These data demonstrate that the duration, intensity and type of signaling alters the sensitivity of T-cells to powerful immunological modifying agents like TGF-beta1.
DescriptionTo access publisher full text version of this article. Please click on the hyperlink in Additional Links field
- CD28 co-stimulation regulates the effect of transforming growth factor-beta1 on the proliferation of naïve CD4+ T cells.
- Authors: Sung JL, Lin JT, Gorham JD
- Issue date: 2003 Feb
- Naive human T-cells become non-responsive towards anti-TNFalpha (infliximab) treatment in vitro if co-stimulated through CD28.
- Authors: Gunnlaugsdottir B, Skaftadottir I, Ludviksson BR
- Issue date: 2008 Dec
- The capacity of the natural ligands for CD28 to drive IL-4 expression in naïve and antigen-primed CD4+ and CD8+ T cells.
- Authors: Bian Y, Hiraoka S, Tomura M, Zhou XY, Yashiro-Ohtani Y, Mori Y, Shimizu J, Ono S, Dunussi-Joannopoulos K, Wolf S, Fujiwara H
- Issue date: 2005 Jan
- Stimulation via the CD3 and CD28 molecules induces responsiveness to IL-4 in CD4+CD29+CD45R- memory T lymphocytes.
- Authors: Damle NK, Doyle LV
- Issue date: 1989 Sep 15
- Modulation of cord blood CD8+ T-cell effector differentiation by TGF-beta1 and 4-1BB costimulation.
- Authors: Kim YJ, Stringfield TM, Chen Y, Broxmeyer HE
- Issue date: 2005 Jan 1