Immunbiologische Effekte der extrakorporalen Photopherese

Zusammenfassung

Die extrakorporale Photopherese (ECP) ist eine Therapiemodalität, bei der mit 8-Methoxypsoralen (8-MOP) behandelte lymphomononukleäre Zellen mit UVA-Licht bestrahlt werden. Die bisher bekannten immunbiologischen Effekte der ECP können in kurz- und längerfristige eingeordnet werden. Unmittelbar nach ECP sind Apoptosevorgänge bei bestrahlten 8-MOP-beladenen Lymphozyten der dominierende Prozess. Daneben kommt es durch den unmittelbaren Kontakt von antigenpräsentierenden Zellen mit dem ECP-Durchfluss-System zu einer Aktivierung und Differenzierung von dendritischen Zellen. Der Differenzierungsprozess wird vermutlich auch durch Zytokininduktion und apoptotische Lymphozyten beeinflusst. Je nach zugrundeliegender Erkrankung beeinflussen die jeweiligen immunologischen Grundsituationen die weitere Wirkung der ECP. Beim kutanen T-Zell-Lymphom kommt dem Vorgang der Transimmunisierung eine besondere Bedeutung zu. Die Aufnahme von malignen apoptotischen Lymphozyten durch unreife dendritische Zellen, die Prozessierung von antigenen Tumorpeptiden und eine nachfolgende spezifische CD8⁺-Immunantwort sind dabei von zentraler Bedeutung. Das klinische Ansprechen korreliert hierbei mit der Tumorlast an malignen T-Zellen im peripheren Blut. Bei der chronischen GvHD-Reaktion konnte gezeigt werden, dass die ECP die Differenzierung von dendritischen Zellen vom DC2-Typ fördert und damit die Alloreaktivität von zytotoxischen T-Zellen beeinflusst. Die biomodulatorischen Effekte der ECP beeinflussen somit nicht nur Lymphozyten, sondern auch antigenpräsentierende Zellen mit ihren regulatorischen Eigenschaften und ihren Einflüssen auf die Gesamtimmunität des Organismus.

Abstract

Extracorporeal photopheresis (ECP) is a therapy in which 8-methoxypsoralen (8-MOP) containing peripheral mononuclear cells is exposed to a long wavelength ultraviolet radiation (UVA) in an extracorporeal system. Immunobiological effects by the ECP can be filed in short- and long-term processes. Immediately after UVA irradiation of the buffy coat, apoptosis of lymphocytes is the dominating processes. Next to it, the direct contact of antigen-presenting cells with the plastic material of ECP device induces activation and differentiation of dendritic cells. In addition, this differentiation process is probably influenced by induction of cytokines and phagocytosis of apoptotic lymphocytes. The general effect of the ECP also depends on the immunological situation of the treated patient. In cutaneous T-cell lymphoma (CTCL) the ECP-induced process of transimmunisation is of particular relevance, including the uptake of apoptotic lymphocytes by immature dendritic cells, processing and presentation of tumorantigens and stimulation of a specific CD8⁺ cytotoxic immune response. Thereby, the clinical response of the ECP correlates with the tumor burden of the peripheral blood. In cutaneous graft-vs-host disease (cGvHD) it has been shown that ECP promotes differentiation of dendritic cells of the DC2 type and, therefore, influences the alloreactivity of cytotoxic T-cells. The bio modulating effects of ECP are, as a consequence, not only directed to lymphocytes but also influence antigen-presenting-cells, their regulatory properties and, therefore, the whole immunological situation of the organism.

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