Send to

Choose Destination
See comment in PubMed Commons below
Transpl Immunol. 2003 Jul-Sep;11(3-4):323-33.

Generation of antigen-specific, interleukin-10-producing T-cells using dendritic cell stimulation and steroid hormone conditioning.

Author information

Department of Internal Medicine, Division of Nephrology, Mayo Clinic and Foundation, 200 First St. SW, Charlton 10 Transplant Center, Rochester, MN 55905, USA.


The mechanisms by which regulatory T-cell populations are generated in vivo are poorly understood. Nonetheless, the possibility of generating T-cells with regulatory capacity ex vivo using pharmacologic agents or modified antigen presenting cells has been raised by a number of recent studies. In this study, the effect of combined glucocorticoid and 1,25 dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) agonists on dendritic cell (DC)-stimulated, antigen-specific CD4(+ve) T-cells was investigated. Following multiple rounds of DC-mediated stimulation in the presence of dexamethasone and an analog of 1,25(OH)(2)D(3), the resulting T-cells were characterized by: (a) enhanced IL-10 secretion upon subsequent antigen exposure, (b) attenuated secretion of IL-2 and interferon gamma, (c) lack of induction of Th2 (IL-4-secreting) phenotype, (d) significant antigen-specific suppression of primary T-cell proliferation and (e) retention of the ability to survive and proliferate to antigen in vivo. These IL-10-secreting T-cells were termed 'steroid hormone-conditioned T-cells'. When a co-stimulation-deficient population of DCs was employed for the in vitro, steroid hormone-conditioned stimulations, two additional effects were observed: (a) a further skewing towards antigen-specific IL-10 production and (b) enhanced activation-induced up-regulation of the inhibitory receptor CTLA-4 (CD152). It was concluded that DC-mediated generation of antigen-specific T-cells in vitro can be modulated to promote an IL-10-secreting, regulatory T-cell population using glucocorticoid and 1,25(OH)(2)D(3) agonists. This T-cell phenotype can be further enhanced by the use of co-stimulation-deficient DCs.

[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center