Photochemotherapy induces a faster apoptosis of alloreactive activated T cells than of nonalloreactive resting T cells in graft versus host disease.
BACKGROUND
Graft versus host disease (GvHD) is the main complication after hematopoietic stem-cell transplantation.Extracorporeal photochemotherapy (ECP) is a cell therapy currently used for the treatment of T-cell–mediated diseases and seems as a valuable second-line therapy for patients suffering from steroid-refractory acute or chronic GvHD. ECP induces the apoptosis of treated cells and is believed to elicit a specific immune regulation of alloreactive T cells through repeated apoptotic T-cell infusions. However, its mechanisms of action have not yet been elucidated. In GvHD,alloreactive but not non alloreactive T cells are continuously activated by their environment. We hypothesized that ECP has a differential apoptotic effect on activated compared with resting T cells.


METHODS
The ECP-induced apoptosis of resting and activated T cells from patients with chronic GvHD was assessed.The kinetic of apoptosis was also evaluated using several triggers of T-cell activation such as mitogenic or antigen specific activation. The influence of survival cytokines (interleukin-2, -7, and -15) was also evaluated.


RESULTS
Activated T cells from patients with chronic GvHD underwent apoptosis faster than resting T cells. This phenomenon was confirmed using mitogenic and antigen-specific activated T cells from healthy donors and cannot be delayed by protective cytokines.


CONCLUSIONS
ECP induces a faster apoptosis of alloreactive activated T cells than of non alloreactive resting T cells in GvHD and more generally of activated T cells than of resting T cells. These novel findings provide new insights about the ECP-induced specific control of pathogenic T cells in GvHD.
INSERM, U823, Immunobiologie et Immunotherapie des Cancers,Grenoble, France.
Dalil
D
Hannani
Etienne
E
Merlin
Françoise
F
Gabert
David
D
Laurin
François
F
Deméocq
Laurence
L
Chaperot
Justyna
J
Kanold
Joel
J
Plumas
D017209:Apoptosis; D002908:Chronic Disease; D016207:Cytokines / Q000276:immunology; D006086:Graft vs Host Disease / Q000209:etiology* / Q000276:immunology / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D008213:Lymphocyte Activation; D017710:Lymphocyte Transfusion; D017893:Photopheresis / Q000009:adverse effects*; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
D016207:Cytokines