A simplified extracorporeal photopheresis procedure based on single high-dose ultraviolet A light irradiation shows similar in vitro efficacy.
BACKGROUND
Extracorporeal photopheresis (ECP) is one of the most widely used and effective cell-based therapies for the treatment of T-cell-mediated diseases. The patients' white blood cells (WBCs) are collected by apheresis and exposed to the photosensitizer 8-methoxypsoralen (8-MOP) and ultraviolet A (UVA) light before retransfusion. The UVA/8-MOP combination has been in use in ECP for more than 4 decades; however, whether ECP can be simplified by UVA light irradiation only has never been analyzed.


STUDY DESIGN AND METHODS
Peripheral blood mononuclear cells were treated with classical ECP or different UVA light doses only (UVAonly ). Treatment efficacy was investigated by apoptosis induction in WBC subsets, inhibition of T-cell proliferation, and the ability of monocytes to induce allogeneic T-cell expansion and to respond to lipopolysaccharide and interferon-γ stimulation in vitro.


RESULTS
High-dose UVAonly treatment (5 J/cm2 ) was as efficient as ECP to induce apoptosis within 48 hours. UVAonly treatment modulated the composition of the surviving cells by improving monocyte survival and promoting CD8+ T-cell apoptosis. Both ECP and UVAonly treatment inhibited anti-CD3/anti-CD28 triggered T-cell proliferation. Interestingly, whereas ECP-treated monocytes exhibited a markedly reduced capacity to respond to stimulation and to induce allogeneic T-cell proliferation, UVAonly treatment preserved monocyte functionality to some degree.


CONCLUSIONS
High-dose UVAonly and standard ECP showed comparable efficacy in inducing apoptosis and inhibiting direct T-cell proliferation. Hence, UVAonly treatment can be a simplified alternative to ECP therapy. Furthermore, increased monocyte survival with partially preserved functionality after UVAonly treatment may provide a novel method for immunoregulation.
['Buchele|Vera|V|0000-0001-7853-3059', 'Hackstein|Holger|H|0000-0001-9722-8180']
D017209:Apoptosis D018106:CD28 Antigens D017252:CD3 Complex D049109:Cell Proliferation D002470:Cell Survival D006801:Humans D066298:In Vitro Techniques D007371:Interferon-gamma D007963:Leukocytes, Mononuclear D008070:Lipopolysaccharides D008730:Methoxsalen D009000:Monocytes D017893:Photopheresis D013601:T-Lymphocytes D014466:Ultraviolet Rays
extracorporeal photopheresis UVA light apoptosis