Photochemotherapy Induces a Faster Apoptosis of Alloreactive Activated T Cells Than of Nonalloreactive Resting T Cells in Graft Versus Host Disease
Résumé
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 nonalloreactive T cells are continuously activated by their environment. We hypothesized that ECP has a differential apoptotic effect on activated compared with resting T cells. Method. 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 nonalloreactive 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.
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2010 - Hannani - Transplantation B.pdf (278 Ko)
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2010 - Hannani - Transplantation B - Figures.pdf (330.75 Ko)
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