Generation of antigen-specific, interleukin-10-producing T-cells using dendritic cell stimulation and steroid hormone conditioning.
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.
Dong
Xiangyang
X
Department of Internal Medicine, Division of Nephrology, Mayo Clinic and Foundation, 200 First St. SW, Charlton 10 Transplant Center, Rochester, MN 55905, USA.
Bachman
Lori A
LA
Kumar
Rajiv
R
Griffin
Matthew D
MD
D000818:Animals; D000941:Antigens / Q000276:immunology; D001854:Bone Marrow Cells / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000494:pharmacology; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000276:immunology*; D005938:Glucocorticoids / Q000494:pharmacology*; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000276:immunology; D051379:Mice; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
D000941:Antigens; D005938:Glucocorticoids; D016753:Interleukin-10; D002117:Calcitriol