<i>In vitro</i> effects of different 8-methoxypsoralen treatment protocols for extracorporeal photopheresis on mononuclear cells

Holger Budde; Ulrike Berntsch; Joachim Riggert; Tobias J. Legler

doi:10.5114/ceji.2017.67312

eISSN: 1644-4124
ISSN: 1426-3912

Central European Journal of Immunology

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1/2017
vol. 42

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abstract:

Experimental immunology

In vitro effects of different 8-methoxypsoralen treatment protocols for extracorporeal photopheresis on mononuclear cells

Holger Budde

,

Ulrike Berntsch

,

Joachim Riggert

,

Tobias J. Legler

(Cent Eur J Immunol 2017; 42 (1): 1-9)

DOI: https://doi.org/10.5114/ceji.2017.67312

Online publish date: 2017/05/08

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Extracorporeal photopheresis (ECP) is an important second-line therapy for graft-versus-host disease. A central therapeutic mechanism is the induction of immune tolerance through apoptosis in patient’s leukocytes, caused by ex vivo incubation with 8-methoxypsoralen (8-MOP) and subsequent UVA irradiation.

We hypothesized that different 8-MOP incubation times and an additional 8-MOP removal step could influence the apoptosis kinetics of leukocytes in general and in particular could lead to different apoptotic levels in the leukocyte subpopulations. After 8-MOP/UVA treatment of human leukocytes, cells were cultured and the percentage of annexin V positive cells from several leukocyte subpopulations was determined. Only regulatory T cells (Tregs) were relatively resistant to 8-MOP/UVA induced apoptosis. When cells were incubated for 30 minutes with 8-MOP prior to UVA exposure, higher percentages of annexin V positive cells were detected on day 1 and day 2 after treatment. Removal of 8-MOP after UVA exposure caused no significant changes in the apoptosis kinetics during the 72 h culture period compared with unwashed cells. The results of our in vitro study indicate that it could be possible to adjust the apoptosis kinetics via modulation of the 8-MOP incubation time. In further in vivo studies it should be elucidated to which extent different apoptosis kinetics influence the therapeutic effect of ECP since steady-state apoptosis levels are probably important for establishing a long lasting immune tolerance. Furthermore we found that Tregs, according to their well-known tolerogenic function, are more resistant to apoptosis after 8-MOP/UVA treatment compared to GvHD inducing T cell populations.

keywords:

In vitro effects of different 8-methoxypsoralen treatment protocols for extracorporeal photopheresis on mononuclear cells

Holger Budde , Ulrike Berntsch , Joachim Riggert , Tobias J. Legler

apoptosis, regulatory T cells (Tregs), photopheresis

Holger Budde

,

Ulrike Berntsch

,

Joachim Riggert

,

Tobias J. Legler