Redirection of human autoreactive T-cells upon interaction with dendritic cells modulated by TX527, an analog of 1,25 dihydroxyvitamin D3

Astrid G.S. Van Halteren, Evelyne Van Etten, Esther C. De Jong, Roger Bouillon, Bart O. Roep, Chantal Mathieu

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

176 Citaten (Scopus)

Samenvatting

The active form of vitamin D3, 1(α,25-dihydroxyvitamin D3 (1,25(OH)2D3), is a potent immunomodulator known to affect T-cells through targeting antigen-presenting cells such as dendritic cells (DCs). We studied the effects of a novel nonhypercalcemic 1,25(OH)2D2 analog, TX527, on DC differentiation, maturation, and function with respect to stimulation of a committed human GAD65-specific autoreactive T-cell clone. Continuous addition of TX527 impaired interleukin (IL)-4 and granulocyte/macrophage colony-stimulating factor (GM-CSF)-driven DC differentiation as well as lipopolysaccharide (LPS) and interferon-γ (IFN-γ)-induced maturation into Th1-promoting DC (DC1), as characterized by marked changes in DC morphology and abrogation of IL-12p7O release upon CD40 ligation. Addition of TX527 during maturation did not affect DC morphology but significantly changed DC cytokine profiles. The potential of treated DCs to alter the response pattern of committed autoreactive T-cells was found to depend on the timing of TX527 exposure. Continuously TX527-treated DCs significantly inhibited T-cell proliferation and blocked IFN-γ, IL-10, but not IL-13 production, whereas DCs treated during maturation failed to inhibit T-cell proliferation but affected IL-10 and IFN-γ production. Collectively, we provide evidence that nonhypercalcemic TX527 is a potent in vitro DC modulator, yielding DCs with the potential to change cytokine responses of committed autoreactive T-cells.

Originele taal-2Engels
Pagina's (van-tot)2119-2125
Aantal pagina's7
TijdschriftDiabetes
Volume51
Nummer van het tijdschrift7
DOI's
StatusGepubliceerd - 2002
Extern gepubliceerdJa

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