Photochemotherapy induces the apoptosis of monocytes without impairing their function.
BACKGROUND
Extracorporeal photopheresis (ECP) is a powerful therapy currently used to treat various hematological disorders as in graft versus host disease. Clinical data clearly demonstrate its efficacy and immunomodulation toward the pathogenic T cells. However, ECP mechanism of action is still poorly understood. Monocytes represent up to 30% of the total amount of treated cells and are known to play an important role in adaptive immunity. However, data from previous reports analyzing the effect of psoralen and UV-A irradiation (PUVA) on their functions are heterogeneous. In this study, we focused on the effect of PUVA on human monocytes functions in adaptive immunity.


METHODS
Purified human monocytes were treated in vitro by PUVA. We measured their kinetic of apoptosis after the treatment. We also determine whether their phenotype and functionalities were modified. Finally, we assessed the functionalities of PUVA-treated monocytes-derived dendritic cells (DC).


RESULTS
PUVA treatment sentenced purified monocytes to die in 6 days and immediately altered their migratory capacities without impairing their ability of endocytosis. It also up-regulated co-stimulatory molecules and production of inflammatory cytokines on activation and consequently stimulated allogeneic or autologous T cells as efficiently as untreated monocytes. Moreover, PUVA-treated monocytes retained their ability to differentiate into fully functional DC that maturated and stimulated T cells as well as normal DC.


CONCLUSIONS
Our data demonstrate that monocytes undergo apoptosis and loose a part of their migratory capacity after ECP and the surviving cell functionalities are not impaired, suggesting that monocytes have a minor effect on ECP-mediated immunomodulation.
Hannani
Dalil
D
Inserm, U823, Immunobiologie et Immunotherapie des cancers, La Tronche, France.
Gabert
Françoise
F
Laurin
David
D
Sall
Mariam
M
Molens
Jean-Paul
JP
Hequet
Olivier
O
Chaperot
Laurence
L
Plumas
Joel
J
D056704:Adaptive Immunity; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D018929:Cell Culture Techniques / Q000379:methods; D016923:Cell Death; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000502:physiology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000528:radiation effects; D006801:Humans; D016130:Immunophenotyping; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000502:physiology; D016260:Monocytes, Activated Killer / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D011701:PUVA Therapy / Q000379:methods; D010778:Photochemotherapy / Q000379:methods*; D017893:Photopheresis / Q000379:methods; D012016:Reference Values