Extracorporeal photochemotherapy (ECP) is a cell based procedure effective in the treatment of different T-cell mediated diseases such as cutaneous T-cell lymphoma and Graft-versus-Host Disease. During ECP treatment the patient’s blood is processed by means of a cell separator to collect leukocytes which are then added with the photoactive drug 8-methoxypsoralen (8-MOP), exposed to ultraviolet-A light (UV-A) and reinfused into the patient. Even if the mechanisms of action of ECP remain elusive, it has been shown to own in-vivo immunomodulatory effects and to be effective also on experimental allergic encephalomyelitis (EAE) animals and in a small pilot study on multiple sclerosis (MS) patients. It has been suggested that during ECP not only UV-A irradiation but also changes in the environmental condition may be relevant. Therefore, we developed a new peristaltic-based bench device which reliably mimics ex-vivo the complete ECP cycle using 50 ml peripheral blood sample. Peripheral blood mononuclear cells (PBMC) were then collected and treated with 8-MOP and/or UV-A under the same conditions used for the patients’ therapy. Using this strategy we investigated 8-MOP and/or UV-A effect on the production of the inflammatory cytokines IFN-γ, IL-2 and TNF-α in PBMC after polyclonal stimulation. We observed a significant decrease in activated CD4+ and CD8+ T-lymphocytes producing cytokines after UV-A irradiation and a further decrease in the presence of 8-MOP. The decrease in cytokines production seemed to be both cytokine- and cell type-related. In fact TNF-α production was reduced to a lesser extent than IFN-γ and IL-2 ones, while CD4+ T-cells seemed to be more sensitive than CD8+ lymphocytes when IFN-gamma and IL-2 production was considered. Both T-cell population showed similar behaviour when TNF-α production was evaluated. Following this preliminary experience, this ex-vivo protocol will be used to deeply investigate the effect of ECP on EAE rats.

Rigolio, R., Perseghin, P., Petersson, J., Biffi, A., Jonsson, S., Cavaletti, G., et al. (2007). Extracorporeal photochemotherapy: early ex-vivo experience on healthy controls and a multiple sclerosis patient to investigate a new potential cell therapy.. In Abstract Book.

Extracorporeal photochemotherapy: early ex-vivo experience on healthy controls and a multiple sclerosis patient to investigate a new potential cell therapy.

RIGOLIO, ROBERTA
Primo
;
CAVALETTI, GUIDO ANGELO
Penultimo
;
2007

Abstract

Extracorporeal photochemotherapy (ECP) is a cell based procedure effective in the treatment of different T-cell mediated diseases such as cutaneous T-cell lymphoma and Graft-versus-Host Disease. During ECP treatment the patient’s blood is processed by means of a cell separator to collect leukocytes which are then added with the photoactive drug 8-methoxypsoralen (8-MOP), exposed to ultraviolet-A light (UV-A) and reinfused into the patient. Even if the mechanisms of action of ECP remain elusive, it has been shown to own in-vivo immunomodulatory effects and to be effective also on experimental allergic encephalomyelitis (EAE) animals and in a small pilot study on multiple sclerosis (MS) patients. It has been suggested that during ECP not only UV-A irradiation but also changes in the environmental condition may be relevant. Therefore, we developed a new peristaltic-based bench device which reliably mimics ex-vivo the complete ECP cycle using 50 ml peripheral blood sample. Peripheral blood mononuclear cells (PBMC) were then collected and treated with 8-MOP and/or UV-A under the same conditions used for the patients’ therapy. Using this strategy we investigated 8-MOP and/or UV-A effect on the production of the inflammatory cytokines IFN-γ, IL-2 and TNF-α in PBMC after polyclonal stimulation. We observed a significant decrease in activated CD4+ and CD8+ T-lymphocytes producing cytokines after UV-A irradiation and a further decrease in the presence of 8-MOP. The decrease in cytokines production seemed to be both cytokine- and cell type-related. In fact TNF-α production was reduced to a lesser extent than IFN-γ and IL-2 ones, while CD4+ T-cells seemed to be more sensitive than CD8+ lymphocytes when IFN-gamma and IL-2 production was considered. Both T-cell population showed similar behaviour when TNF-α production was evaluated. Following this preliminary experience, this ex-vivo protocol will be used to deeply investigate the effect of ECP on EAE rats.
Si
abstract
Scientifica
Extracorporeal Photochemotherapy, peripheral blood cells, T cell cytokine production, multiple sclerosis, healthy controls
English
3rd CELLAID Symposium - Cell therapies for autoimmune diseases
Rigolio, R., Perseghin, P., Petersson, J., Biffi, A., Jonsson, S., Cavaletti, G., et al. (2007). Extracorporeal photochemotherapy: early ex-vivo experience on healthy controls and a multiple sclerosis patient to investigate a new potential cell therapy.. In Abstract Book.
Rigolio, R; Perseghin, P; Petersson, J; Biffi, A; Jonsson, S; Cavaletti, G; Cilio, C
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/60735
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